Pet Stem Cell Therapy

Wildlife trafficking, which is the illegal trade of wild animals and plants, either as dead or live specimens, or their parts, has a huge negative effect on the worlds environments, biodiversity, economies, governance, and health. It is a form of transnational organised crime that spans across many countries and involves poaching, smuggling, and illegal collection or capture, of protected wildlife.

According to the World Wildlife Fund (WWF), wildlife trafficking is the fourth largest form of transnational organised crime (after smuggling of drugs, human trafficking, and counterfeiting) worth anestimated 15 billion per annum.

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Despite being a part of theCITES(Convention on International Trade in Endangered Species of wild fauna and flora), India is currently one among thetop 20 countriesfor wildlife trafficking, and among thetop 10 for wildlife trafficking by air. Due to its megadiverse nature (India has 8% of the worlds wildlife), and dense human population (which makes tracing illegal goods very difficult once they have entered domestic markets), India serves as both, a source, as well as a transit country for illegal wildlife and wildlife products.

Added to this, several other factors have made the fight against the illegal wildlife trade increasingly difficult. Amongst these are the porous international borders with China, Myanmar, and other Southeast Asian countries, agrowing aviation marketand thefast-expanding airport sector, and theuse of social media as online marketplacesby wildlife traffickers.

Furthermore, smugglers of exotic wildlife species in India have even resorted tomisusing the Voluntary Disclosure Schemeissued by the Ministry of Environment, Forest and Climate Change (MoEFCC) in 2020. Theschemeaimed to regulate the growing market of exotic animals in India which boomed after the complete ban on trade in Indian species by allowing Indians to declare the possession of exotic wild species without any documentation before March 15, 2021.

Besides these reasons, there are majorlacunae in lawsthat pertain to the ownership of exotic animals in India. People caught transporting exotic wildlife species can be charged with the crime only if it can be proven that they crossed an international border illegally with those animals. Once inside India, there are no policies or laws that regulate the ownership of exotic species. The Wildlife Protection Law only applies to Indian wildlife, says Sanjeev Pednekar, founder of Prani,an education centre and pet sanctuaryfor rescued birds and animals in the outskirts of Bengaluru.

Since India is not only a major source, but also a transit, and destination country for trafficked wildlife and wildlife products, a large number of species are illegally transported out of and into the country. According to theSmuggling in India report 202021, the DRIs (Directorate of Revenue Intelligence) most common wildlife and wildlife products that were seized from being smuggled out of India are ivory, turtles and tortoises (especially the Indian star tortoise), and red sandalwood (red sanders orlalchandan). Lately, there has been a decline in rhino horn trading from India; however, the country is fast becoming a major hub forpangolin poaching and trafficking. The trade in tiger parts also seems to becontinuing unabated.

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In addition, ornamental fish such as theChanna barca or snakehead(endemic to the upper Brahmaputra basin) and thezebra loach(in the Western Ghats) are being fished to extinction in their natural habitats to feed the international trade in live aquarium fish. Along with these, wildlife trafficking has expanded to include trade in body parts ofgolden jackals,Asiatic black bears,leopards(for tantric uses and traditional medicines) andmongooses(for mongoose hair paintbrushes).

According to the Trade Records Analysis of Flora and Fauna in Commerce (TRAFFIC)Runway to Extinction reportpublished in 2020, although the trafficking of Indian star tortoises out of India is declining, the smuggling of red eared slider turtles is on the rise. Instances of exotic animals such as kangaroos, marmosets, tamarins, and birds such as macaws and parrots being transported across India areon the rise. The latest in this string of reports rolled in during March and April 2022, with videos of dehydrated and sickkangaroos rescued in West Bengal.

Apart from the illegal import and export of wildlife and wildlife products, India also has a roaring domestic market for wildlife meat and body parts for traditional medicine, including those offreshwater turtles,lorises, andfrogs.

International wildlife trafficking into and out of India mainly occurs through two routes one, through the long international border along the Northeast, and the other, through airports. The 2018 TRAFFIC reportIn Plane Sightnotes that trafficking in rhino horns, tiger parts, and pangolin scales is especially rampant in the Indo-Nepal, and Indo-Myanmar-China borders, with Northeast Indian cities such as Dimapur, Guwahati and Imphal being used a transit sites. Trafficking of birds and reptiles along the India-Bangladesh border is also rampant. Most recently, the Dooars region in northern West Bengal, specifically, the town of Jalpaiguri, made news as an emerging transit point for trafficking of exotic animals and birds.

Thetrafficking of reptiles, specifically turtles and tortoises, into and out of India is especially rampant, with Chennai and Mumbai airports being major hubs for this activity. The Indian star tortoise, which is the most trafficked reptile in the world, is supplied from trade hubs in Karnataka,Andhra Pradesh, Gujarat, and Tamil Nadu, to Thailand, Singapore, and Malaysia, primarily by air. Seizure data from the website Reducing Opportunities for Unlawful Trade of Endangered Species (ROUTES) shows that more than 54% of the trafficked animals were inchecked-in luggageand about 11% inair cargo. The top Indian cities where such airport seizures happen include Chennai, Kolkata, Mumbai, and Delhi, with reptile seizures being especially high in Chennai airport.

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Wildlife trafficking in India is driven by many factors. The foremost of these is the demand for raw material like red sandalwood and ivory (used in manufacturing luxury products), and animal parts particularly rhinoceros horn and tiger parts for traditional medicine. TheWorld Wildlife Crime Report 2020states that although global markets for rhino horn and ivory have fallen consistently since 2011, new market demands such as those for pangolin scales and European glass eels have emerged. In Assam, because ofintense hunting of pangolins by local tribes, which eat the meat and sell the scales, this once-abundant animal is now relatively rare. The traditional medicine markets in China and Vietnam are major consumers of pangolin scales, rhino horns, and the skin and body parts of various big cats, birds, Asiatic black bears, musk deer, wolves, and jackals.

Another factor that drives wildlife trafficking is the demand for meat many animals such as theBengal slow loris,softshell turtles from Uttar Pradesh, deer, antelope, wild cattle, and even sea cucumbers are mainly trafficked for consumption.

The third major driving factor for wildlife trafficking in India lies in thegrowing demand for exotic pets,especially birdslike cockatoos, macaws, and grey parrots. In addition many Indianbirds,fish, andreptilesare in great demand in global pet markets. What is even more shocking, is that zoos may also be involved in illegally buying exotic animals, as per a recent caseinvolving Indore zoo and its connection to kangaroosbeing transported from a farm in Mizoram.

The wildlife trade not only depletes environments of their natural inhabitants, but is also responsible foradded threats like the spread of invasive species and emergence of new zoonoses. The three factors in combination can leadto whole ecosystem collapsesand major disease outbreaks. Some of the most virulent viral diseases including Ebola, Marburg virus disease, SARS (Severe Acute Respiratory Syndrome), and the most recent pandemic COVID-19 (Coronavirus disease-19) have all arisen in areas where close human-wildlife contact occurred such as inwet markets.

Wildlife trafficking in India is rapidly wiping out populations of tigers, elephants, rhinos, pangolins, star tortoises, and many other native species. Simultaneously, invasive species like thered eared slider turtles(which are popular pets) andsuckermouth sailfin catfish(a common aquarium fish) are destroying natural habitats.

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The DRI, which is in the forefront of thebattle against smuggling, has teamed up with the Indian Customs as a part of theGreen Customs initiativeof the World Customs Organisation, to counter wildlife trafficking into and out of India. To combat the rising use of air transport in wildlife trafficking,a suite of toolsto help law enforcement agencies in India battle wildlife smuggling have been developed by TRAFFIC, along with the United Nations Environment Programme (UNEP), World Wildlife Fund-India (WWF-India), and theWildlife Crime Control Bureau(WCCB).

Apart from this, the International Air Transport Association (IATA) also has ashort 20-minute training moduleto help spread awareness on wildlife trafficking through air transport. Airport authorities in Bengaluru have even set up aforest cellto tackle wildlife smuggling. TheCounter Wildlife Trafficking program, run by the Wildlife Conservation Society-India, conducts training and sensitisation workshops for state forest departments, police forces, customs officials, border security force units, and even the judiciary, on conducting crime scene investigations and promoting inter-agency collaborations.

In addition to all these initiatives, the WCCB hasbegun profiling criminalsin a real-time database and will soon network with neighbouring countries (Nepal, Bhutan, Bangladesh, and Myanmar) to stem transboundary wildlife crime.

Molecular biology tools, includingDNA testingand bioinformatics are also being used in wildlife forensics to identify thepoint of origin of trafficked animal products. In addition, citizen science initiatives,dog squads, and various DNAdatabasesandreference librariesare being used to monitor animal populations susceptible to poaching and the wildlife trade. India alsodestroys seized wildlife productsto send out a strong anti-poaching message.

However, despite these efforts wildlife trafficking in India is still rampant. Indias CITES membership as well asits strong laws(Wildlife Protection Act, 1972) prohibiting the trade of over 1,800 species of native plants, animals, and their products are ineffective in tackling wildlife trafficking as these laws/advisories are often poorly communicated and enforced. In addition, wildlife experts say that India needsstronger laws to deal with exotic speciesthat have been smuggled into the country, which is a huge lacuna that is exploited by smugglers to feed the exotic pet trade.

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Most often, when exotic live animals that have been smuggled into India are seized, they are sent to rescue centres or sanctuaries. Since zoos are usually meant to showcase Indian native wildlife, they often do not have adequate quarantine centres or appropriate enclosures to properly manage seized exotic animals.

Sanjeevs sanctuary, Prani, currently houses many exotics iguanas, monitor lizards, red-eared sliders, and emus to name a few. Nearly 90% of the exotic birds that we have at Prani, along with our iguanas, were given up by people who could no longer care for them. Sometimes, we also rescue animals meant for slaughter, such as our emus, says Sanjeev. In addition, Prani also has also been working/volunteering with the airport authorities in Bengaluru, the Forest Department, and the Animal Welfare Board of India, who often hand over seized animals to us. One memorable instance that stands out in my mind was when we had to care for over a hundred tiny Hamilton turtles one of the most endangered species of turtles in the world that were seized at the Kempegowda International Airport, he adds.

Sanjeev ruefully admits that he often takes in red eared sliders out of fear that people will abandon them in local lakes and ponds, where these terrapins can destroy the ecosystem and kill off native species. Since theCITES rulesdo not usually allow for reintroduction of exotic species to their natural habitats (except under very stringent circumstances), humane euthanasia or a lifetime of captive care are the only ways to deal with smuggled exotics.

Since most people will not even entertain the idea of euthanasia, most exotics are usually condemned to life in captivity. And so many of the exotic species smuggled into India such as capuchins, marmosets, and wallabies, which fetch good sums when sold are returned to the pet market, while others, like the red eared sliders are either given up to rescue centres or subject to uncontrolled releases, he adds.

Also read: Heres why ADHD can make it harder to keep eating habits in check

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Has Another Restaurant Show Come to Loveland to Make People Cry? – Retro 102.5

A couple of 'restaurant' shows have come to Loveland in the last year, and now it seems as though another one is here to do their thing.

It was in October of 2021, that 'Restaurant Impossible' came to Loveland to help out Casa Real. They did make improvements, though not everyone was keen on what they did.

It's fun when a television show comes to your hometown to film. I grew up in Loveland, and still get giddy when these stories come out. 'OOH! A TV star is coming to Loveland! Cool!' How many different cities/towns do these shows go to, all the time, and face 'yocals' like me? It must be in the hundreds.

Downtown Loveland's The Ball Joint was on The Cooking Channel's 'Food Paradise' in February of 2022, and really gave them a shot in the arm. Publicity, in the form of being on TV, does go a long way. The Ball Joint, however, was just showcasing their unique menu, they weren't getting advice or a renovation.

This new visit sounds like advice and a renovation.

It sounds like Jon Taffer and the gang at Bar Rescue are coming into to help out a long time eatery.I've eaten there, had drinks there, many times. It's a very friendly place with good food. CJ's Patio Grill.

I checked out there Facebook page when I got the lead, and they are indeed closing for a few days.

CJ's-Patio-Grill-Closed

I went over to CJ's on the morning of June 7, 2022. The parking lot had about a dozen parking spaces blocked off around the perimeter of the lot, and a some staffers were seated outside. A staffer saw me walking up to take a photo; we had a discussion:

We're closed.

I heard that Bar Rescue is coming, is that true?

I can't say... Non-Disclosure Agreement...

Here we are with another 'NDA' for the Fort Collins area.Interesting, no? I hope that things aren't in terrible shape for CJ's; I've seen Bar Rescue, and when Jon comes to your place, he's going to get in somebody's face, probably yours.

In the end, it's going to be great to get in there and see that they changed. I have a few ideas on what they might do, design wise. Hopefully, everybody walks away happy, with little tears shed.

CJ's-Patio-Grill-Loveland

As Loveland looks at 2022, let's look at 22 things the city could use.

Some of these joints have been gone for decades; a few, not that long.

To prepare yourself for a potential incident, always keep your vet's phone number handy, along with an after-hours clinic you can call in an emergency. The ASPCA Animal Poison Control Center also has a hotline you can call at (888) 426-4435 for advice.

Even with all of these resources, however, the best cure for food poisoning is preventing it in the first place. To give you an idea of what human foods can be dangerous, Stacker has put together a slideshow of 30 common foods to avoid. Take a look to see if there are any that surprise you.

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Has Another Restaurant Show Come to Loveland to Make People Cry? - Retro 102.5

MD Anderson researchers present cellular therapy advances at the 2022 ASCO Annual Meeting – EurekAlert

ABSTRACTS 7518, 7509, 8009

Promising clinical results with cellular therapies for patients with blood cancers highlight advances being presented by researchers from The University of Texas MD Anderson Cancer Center at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

These findings include long-term outcomes of patients receiving an infusion of brexucabtagene autoleucel (KTE-X19) for mantle cell lymphoma, efficacy of gamma delta CAR T therapy for aggressive B-cell lymphoma and responses of umbilical cord blood-derived expanded natural killer cells when given together with combination therapy before stem cell transplant.

CAR T cell therapy shows durable responses after three years for patients with mantle cell lymphoma (Abstract 7518)Three-year follow-up data from the Phase II ZUMA-2 trial showed a long-term survival benefit and low disease relapse potential with one infusion of the anti-CD19 chimeric antigen receptor (CAR) T cell therapy brexucabtagene autoleucel (KTE-X19) in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL). Principal investigator Michael Wang, M.D., professor of Lymphoma and Myeloma, presented results from the trial, and study results were published in the Journal of Clinical Oncology.

The updated results include all 68 patients treated with KTE-X19 on the trial with an additional two years of follow-up. After 35.6 months median follow-up, the overall response rate was 91%, with a 68% complete response rate. The median duration of response was 28.2 months, with 25 of 68 treated patients still in ongoing response at data cutoff.

This represents the longest follow-up of CAR T cell therapy in patients with mantle cell lymphoma to date, Wang said. It is encouraging to see this therapy induced durable long-term responses and a low relapse rate for these patients.

All patients had R/R disease after receiving up to five therapies, and all had received previous Brutons tyrosine kinase (BTK) inhibitor therapy. BTK inhibitors have greatly improved outcomes in R/R MCL, yet patients who have subsequent disease progression are likely to have poor outcomes, with median overall survival of just six to 10 months. Few patients in this category qualify to proceed to an allogeneic stem cell transplant.

Response and survival benefits were positive regardless of the prior BTK inhibitor type. Ongoing effectiveness trended lower in patients with prior acalabrutinib exposure. More investigation is needed to determine the mechanism behind these differences. The findings support future study of CD19-directed CAR T cell therapy in patients with high-risk MCL in earlier treatment lines.

The researchers also evaluated minimal residual disease (MRD) as an exploratory endpoint using next-generation sequencing on 29 patients. Of those, 24 were MRD-negative at one month, and 15 of 19 with available data were MRD-negative at six months. Circulating tumor DNA analysis of MRD at three and six months was predictive of disease relapse.

The treatment was well tolerated, as reported in previous studies with this therapy. Only 3% of treatment-emergent adverse events (AE) of interest occurred since the primary report. The most frequent Grade 3 AE was neutropenia.

The study was funded by Kite Pharma, a Gilead Company. Wang has received research support and has served on the advisory board and as a consultant for Kite Pharma. A complete list of collaborating authors can be found within the abstract here.

Allogeneic gamma delta CAR T cell therapy displayed encouraging efficacy in B-cell lymphoma (Abstract 7509)In the Phase 1 GLEAN trial of ADI-001, an anti-CD20 CAR-engineered allogeneic gamma delta T cell product, the treatment was well tolerated and showed continued efficacy in patients with R/R aggressive B-cell lymphoma. Results from the ongoing trial were presented by Sattva Neelapu, M.D., professor ofLymphoma and Myeloma.

The first-in-human trial enrolled ten patients and eight were evaluable and monitored for at least 28 days. The median age was 62 years and patients received a median of 4 prior therapies. At Day 28, the overall response rate (ORR) and complete response (CR) rate based upon PET/CT was 75%. The ORR and CR rate was 80% at dose levels two and three combined. The ORR and CR rate in CAR-T relapsed patients was 100%.

The responses to ADI-001 in this population of heavily pre-treated and refractory lymphoma patients, including in those with prior CD19 CAR T cell therapy, is very promising, Neelapu said. These results suggest the potential for off-the-shelf gamma delta CAR T cell therapy to be an effective treatment possibility for patients with B-cell lymphoma.

While autologous CD19-targeted CAR T cell therapy has been effective in R/R large B-cell lymphoma, there remains a need for alternative cell-based therapies. This study uses a subset of T cells, known as gamma delta 1 T cells, isolated from the peripheral blood of donors as the basis for CAR T cell therapy.

Gamma delta 1 T cells are desirable because they are able to combine both innate and adaptive mechanisms to recognize and kill malignant cells, and high levels of these cells in hematologic and solid tumors are associated with improved clinical outcomes. ADI-001 expresses major histocompatibility complex (MHC)-independent gamma delta T cell receptors, therefore lowering the risk of graft versus host disease (GvHD) without the need for gene editing.

The median age on the study was 62 years, and patients had received a median of 4 prior therapies. The treatment was well tolerated with most related events being grade 1 or 2. There were two cases of cytokine release syndrome and one case of immune effector cell-associated neurotoxicity syndrome. There were no reported cases of GvHD or dose-limiting toxicity.

Enrollment in the trial is ongoing and a potentially pivotal program is planned.

The study was funded by Adicet Bio, Inc. Neelapu has received research support and has served on the advisory board and as a consultant for Adicet Bio and has intellectual property related to cell therapy. A complete list of collaborating authors can be found within the abstract here.

Expanded NK cells combined with chemoimmunotherapy achieved durable responses in multiple myeloma (Abstract 8009)Results from the expansion phase of a Phase II clinical trial demonstrated that umbilical cord blood-derived expanded natural killer (NK) cells combined with chemotherapy and immunotherapies achieved durable responses in patients with multiple myeloma. Results from the completed clinical trial were presented by Samer Srour M.D., assistant professor of Stem Cell Transplantation & Cellular Therapy.

Thirty patients on the trial received NK cells plus elotuzumab (an immunotherapy monoclonal antibody), lenalidomide (an immunomodulatory drug) and high-dose melphalan chemotherapy before autologous stem cell transplant (ASCT).

At three months post-transplant, 97% of patients achieved at least a very good partial response (VGPR), including 76% with a complete response or stringent complete response, while 75% were minimal residual disease (MRD)-negative. At a median follow-up of 26 months, only four patients had progressed. At two years, the progression-free survival rate was 83% and the overall survival rate was 97%.

Patients with high-risk multiple myeloma have more options to treat their disease than previous years, but they continue to have poor outcomes, Srour said. These results indicate excellent hematologic and minimal residual disease responses and improved survival for these patients, suggesting this approach could provide an additional treatment opportunity.

NK cells are white blood cells that monitor the body for virus-infected and cancerous cells. MD Anderson researchers pioneered the approach to isolate and expand NK cells from umbilical cord blood to be used as cellular therapies. Lenalidomide enhances NK cell function and antibody-mediated cell toxicity against tumor targets. Preclinical data showed that lab-expanded NK cells demonstrated higher elotuzumab-mediated cytotoxicity against myeloma targets than non-expanded cells, and that the addition of elotuzumab to lenalidomide amplified the cord blood-NK cell antibody-dependent cellular cytotoxicity against a commonly used cell line to evaluate novel therapies for multiple myeloma (MM1.S) targets.

The study enrolled 30 patients with high-risk multiple myeloma, with a median age of 63. Twenty-nine patients (97%) had Revised Multiple Myeloma International Staging System (R-ISS) stages 2/3, 40% had 2 high-risk genetic abnormalities, and 23% had deletions or mutations of TP53. The primary endpoints were best response rate (VGPR) and MRD three months after ASCT.

Before the ASCT, stem cells are taken from the patient and stored. After treatment with the immunotherapy and chemotherapy drugs, stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

The treatment was well tolerated, with no unexpected serious adverse effects attributable to NK cells noted. The investigators plan to launch a randomized clinical trial to further explore this treatment combination for patients with high-risk multiple myeloma.

This study was supported with funding from the High-Risk Multiple Myeloma Moon Shot, part of MD Andersons Moon Shots Program, a collaborative effort to accelerate the development of scientific discoveries into clinical advances that save patients lives. The research also was supported by Celgene, a Bristol Myers Squibb company.

Srour has no conflicts of interest. A complete list of collaborating authors can be found within the abstract here.

Original post:
MD Anderson researchers present cellular therapy advances at the 2022 ASCO Annual Meeting - EurekAlert

TACSTD2 upregulation is an early reaction to lung infection | Scientific Reports – Nature.com

Lenrt, S. et al. Trop2: Jack of all trades, master of none. Cancers 12, 3328 (2020).

PubMed Central Google Scholar

Remk, J. et al. Trop-2 plasticity is controlled by epithelial-to-mesenchymal transition. Carcinogenesis 39, 14111418 (2018).

PubMed Google Scholar

Linnenbach, A. J. et al. Sequence investigation of the major gastrointestinal tumor-associated antigen gene family, GA733. Proc. Natl. Acad. Sci. U.S.A. 86, 2731 (1989).

ADS CAS PubMed PubMed Central Google Scholar

Linnenbach, A. J. et al. Retroposition in a family of carcinoma-associated antigen genes. Mol. Cell. Biol. 13, 15071515 (1993).

CAS PubMed PubMed Central Google Scholar

El Sewedy, T., Fornaro, M. & Alberti, S. Cloning of the murine TROP2 gene: Conservation of a PIP2-binding sequence in the cytoplasmic domain of TROP-2. Int. J. Cancer 75, 324330 (1998).

PubMed Google Scholar

Lipinski, M., Parks, D. R., Rouse, R. V. & Herzenberg, L. A. Human trophoblast cell-surface antigens defined by monoclonal antibodies. Proc. Natl. Acad. Sci. U.S.A. 78, 51475150 (1981).

ADS CAS PubMed PubMed Central Google Scholar

Stepan, L. P. et al. Expression of Trop2 cell surface glycoprotein in normal and tumor tissues. J. Histochem. Cytochem. 59, 701710 (2011).

CAS PubMed PubMed Central Google Scholar

Trerotola, M. et al. Upregulation of Trop-2 quantitatively stimulates human cancer growth. Oncogene 32, 222233 (2013).

CAS PubMed Google Scholar

Sozo, F., Wallace, M. J., Zahra, V. A., Filby, C. E. & Hooper, S. B. Gene expression profiling during increased fetal lung expansion identifies genes likely to regulate development of the distal airways. Physiol. Genomics 24, 105113 (2006).

CAS PubMed Google Scholar

McDougall, A. R. A. et al. The oncogene Trop2 regulates fetal lung cell proliferation. Am. J. Physiol. Lung Cell. Mol. Physiol. 301, 478489 (2011).

Google Scholar

Mustata, R. C. et al. Identification of Lgr5-independent spheroid-generating progenitors of the mouse fetal intestinal epithelium. Cell Rep. 5, 421432 (2013).

CAS PubMed Google Scholar

Fernandez Vallone, V. et al. Trop2 marks transient gastric fetal epithelium and adult regenerating cells after epithelial damage. Dev. Camb. Engl. 143, 14521463 (2016).

Google Scholar

Sun, W., Wilhelmina Aalders, T. & Oosterwijk, E. Identification of potential bladder progenitor cells in the trigone. Dev. Biol. 393, 8492 (2014).

CAS PubMed Google Scholar

Tsukahara, Y., Tanaka, M. & Miyajima, A. TROP2 expressed in the trunk of the ureteric duct regulates branching morphogenesis during kidney development. PLoS ONE 6, e28607 (2011).

ADS CAS PubMed PubMed Central Google Scholar

McDougall, A. R. A. et al. Intrauterine growth restriction alters the postnatal development of the rat cerebellum. Dev. Neurosci. 39, 215227 (2017).

CAS PubMed Google Scholar

Tsujikawa, M. et al. Identification of the gene responsible for gelatinous drop-like corneal dystrophy. Nat. Genet. 21, 420423 (1999).

CAS PubMed Google Scholar

Takaoka, M., Nakamura, T., Ban, Y. & Kinoshita, S. Phenotypic investigation of cell junction-related proteins in gelatinous drop-like corneal dystrophy. Investig. Ophthalmol. Vis. Sci. 48, 10951101 (2007).

Google Scholar

Aizarani, N. et al. A human liver cell atlas reveals heterogeneity and epithelial progenitors. Nature 572, 199204 (2019).

CAS PubMed PubMed Central Google Scholar

Goldstein, A. S. et al. Trop2 identifies a subpopulation of murine and human prostate basal cells with stem cell characteristics. Proc. Natl. Acad. Sci. U.S.A. 105, 2088220887 (2008).

ADS CAS PubMed PubMed Central Google Scholar

Okabe, M. et al. Potential hepatic stem cells reside in EpCAM+ cells of normal and injured mouse liver. Development 136, 19511960 (2009).

CAS PubMed Google Scholar

Yang, J. et al. Trop2 regulates the proliferation and differentiation of murine compact-bone derived MSCs. Int. J. Oncol. 43, 859867 (2013).

CAS PubMed Google Scholar

Memarzadeh, S. et al. Cell-autonomous activation of the PI3-kinase pathway initiates endometrial cancer from adult uterine epithelium. Proc. Natl. Acad. Sci. U.S.A. 107, 1729817303 (2010).

ADS CAS PubMed PubMed Central Google Scholar

Li, T. et al. Trop2 guarantees cardioprotective effects of cortical bone-derived stem cells on myocardial ischemia/reperfusion injury. Cell Transplant. 27, 12561268 (2018).

PubMed PubMed Central Google Scholar

Wang, J. et al. Loss of Trop2 promotes carcinogenesis and features of epithelial to mesenchymal transition in squamous cell carcinoma. Mol. Cancer Res. 9, 16861695 (2011).

CAS PubMed PubMed Central Google Scholar

Dreyfuss, D. & Ricard, J.-D. Acute lung injury and bacterial infection. Clin. Chest Med. 26, 105112 (2005).

PubMed Google Scholar

GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 19802017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet Lond. Engl. 392, 17361788 (2018).

Google Scholar

Osuka, A., Ogura, H., Ueyama, M., Shimazu, T. & Lederer, J. A. Immune response to traumatic injury: Harmony and discordance of immune system homeostasis. Acute Med. Surg. 1, 6369 (2014).

PubMed PubMed Central Google Scholar

Stoecklein, V. M., Osuka, A. & Lederer, J. A. Trauma equals dangerdamage control by the immune system. J. Leukoc. Biol. 92, 539551 (2012).

CAS PubMed PubMed Central Google Scholar

Huber-Lang, M., Lambris, J. D. & Ward, P. A. Innate immune responses to trauma. Nat. Immunol. 19, 327341 (2018).

CAS PubMed PubMed Central Google Scholar

Vieira Braga, F. A. et al. A cellular census of human lungs identifies novel cell states in health and in asthma. Nat. Med. 25, 11531163 (2019).

CAS PubMed Google Scholar

Travaglini, K. J. et al. A molecular cell atlas of the human lung from single-cell RNA sequencing. Nature 587, 619625 (2020).

ADS CAS PubMed PubMed Central Google Scholar

Yu, Y. et al. A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages. Nat. Commun. 5, 3230 (2014).

ADS PubMed Google Scholar

Angelidis, I. et al. An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics. Nat. Commun. 10, 963 (2019).

ADS PubMed PubMed Central Google Scholar

Kim, E. Y. et al. Persistent activation of an innate immune axis translates respiratory viral infection into chronic lung disease. Nat. Med. 14, 633640 (2008).

CAS PubMed PubMed Central Google Scholar

Liu, Q. et al. Increased expression of TROP2 in airway basal cells potentially contributes to airway remodeling in chronic obstructive pulmonary disease. Respir. Res. 17, 159 (2016).

PubMed PubMed Central Google Scholar

Major, J. et al. Type I and III interferons disrupt lung epithelial repair during recovery from viral infection. Science 369, 712717 (2020).

ADS CAS PubMed PubMed Central Google Scholar

Kamata, H. et al. Epithelial cell-derived secreted and transmembrane 1A signals to activated neutrophils during Pneumococcal pneumonia. Am. J. Respir. Cell Mol. Biol. 55, 407418 (2016).

CAS PubMed PubMed Central Google Scholar

Katsura, H. et al. Human lung stem cell-based alveolospheres provide insights into SARS-CoV-2-mediated interferon responses and pneumocyte dysfunction. Cell Stem Cell 27, 890-904.e8 (2020).

CAS PubMed PubMed Central Google Scholar

Gerlach, R. L., Camp, J. V., Chu, Y.-K. & Jonsson, C. B. Early host responses of seasonal and pandemic influenza A viruses in primary well-differentiated human lung epithelial cells. PLoS ONE 8, e78912 (2013).

ADS PubMed PubMed Central Google Scholar

Shen, B. Q., Finkbeiner, W. E., Wine, J. J., Mrsny, R. J. & Widdicombe, J. H. Calu-3: A human airway epithelial cell line that shows cAMP-dependent Cl-secretion. Am. J. Physiol. 266, L493-501 (1994).

CAS PubMed Google Scholar

Rezaee, F. & Georas, S. N. Breaking barriers. New insights into airway epithelial barrier function in health and disease. Am. J. Respir. Cell Mol. Biol. 50, 857869 (2014).

PubMed PubMed Central Google Scholar

Soong, G., Parker, D., Magargee, M. & Prince, A. S. The type III toxins of Pseudomonas aeruginosa disrupt epithelial barrier function. J. Bacteriol. 190, 28142821 (2008).

CAS PubMed Google Scholar

Short, K. R. et al. Influenza virus damages the alveolar barrier by disrupting epithelial cell tight junctions. Eur. Respir. J. 47, 954966 (2016).

CAS PubMed Google Scholar

Linfield, D. T., Raduka, A., Aghapour, M. & Rezaee, F. Airway tight junctions as targets of viral infections. Tissue Barriers 9, 1883965 (2021).

PubMed PubMed Central Google Scholar

Nakatsukasa, M. et al. Tumor-associated calcium signal transducer 2 is required for the proper subcellular localization of claudin 1 and 7: Implications in the pathogenesis of gelatinous drop-like corneal dystrophy. Am. J. Pathol. 177, 13441355 (2010).

CAS PubMed PubMed Central Google Scholar

Xu, P. et al. A new in vitro model of GDLD by knocking out TACSTD2 and its paralogous gene EpCAM in human corneal epithelial cells. Transl. Vis. Sci. Technol. 7, 30 (2018).

CAS PubMed PubMed Central Google Scholar

Nakato, G. et al. Amelioration of congenital tufting enteropathy in EpCAM (TROP1)-deficient mice via heterotopic expression of TROP2 in Intestinal EPITHELIAL cells. Cells 9, 1847 (2020).

CAS PubMed Central Google Scholar

Singh, R. et al. A new triglycyl peptide linker for antibody-drug conjugates (ADCs) with improved targeted killing of cancer cells. Mol. Cancer Ther. 15, 13111320 (2016).

CAS PubMed Google Scholar

Szala, S. et al. Molecular cloning of cDNA for the carcinoma-associated antigen GA733-2. Proc. Natl. Acad. Sci. 87, 35423546 (1990).

ADS CAS PubMed PubMed Central Google Scholar

Mashhadi, S. M. Y. et al. Shedding light on the EpCAM: An overview. J. Cell. Physiol. 234, 1256912580 (2019).

Google Scholar

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TACSTD2 upregulation is an early reaction to lung infection | Scientific Reports - Nature.com

‘Unnatural selection’: How humans are altering the evolution of other animals – Genetic Literacy Project

June 1, 2022 admin Pet Stem Cell Therapy

The bouncing orange specks could be popcorn dancing on a hot plate. But theres something odd about how they move. Individual kernels spin in tight circles. Pairs slow dance a pas de deux. A cluster performs one full rotation counter-clockwise before dispersing. Each collision sets off a new motion. They seem to bebehaving.

What look like popcorn kernels inthis short videoare in fact a swarm of microscopic xenobots: tiny living robots, assembled from frog cells.

While living robots might seem a strange concept, in fact the first robots were made of flesh, not metal. Theword was coined in 1921, in a play by Czech playwright Karel apek.Rossums Universal Robotswas a thought experiment along the lines of Mary Shelleys Frankenstein, about a scientists desire to create artificial people. Nature has found only one method of organising living matter, declares Rossum, the scientist in question. There is, however, another method, more simple, flexible and rapid which has not yet occurred to nature at all.

Imagine him sitting over a test tube and thinking how the whole tree of life would grow from him, says another character.

In the century that followed, however, robots developed as things of steel and wire, rather than living tissue. Engineering moved faster than biology, says Douglas Blackiston, a developmental biologist at Tufts University. But biology is rapidly catching up. Blackiston is one of a team of scientists designing xenobots: tiny living robots, painstakingly constructed from tissue harvested fromXenopus laevis, the African clawed frog.

Thefirst xenobotswere revealed to the world at the start of 2020: minuscule cubes formed of skin cells and propelled by two stubby legs made of heart muscle. They were designed by a computer algorithm and hand-built by researchers with the objective to make the xenobots walk. (In a pleasing coincidenceXenopus means strange foot.) These organic automatons could also work together to move particles around their environment, and unlike mechanical robots they self-healed when injured.

Autolus Therapeutics to Present Four Clinical Data Updates at the European Hematology Association Congress – GlobeNewswire

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Autolus Therapeutics to Present Four Clinical Data Updates at the European Hematology Association Congress - GlobeNewswire

- AUTO4: oral presentation on initial clinical experience in peripheral T cell lymphoma- AUTO1/22: oral presentation on initial experience in r/r pediatric B-cell acute lymphoblastic leukemia- obe-cel: poster presentation in r/r primary CNS lymphoma- obe-cel: poster presentation in r/r B-non-Hodgkins lymphoma and chronic lymphoblastic leukemia- Conference call to be held on June 13, 2022 at 7:30 am EST/12:30 pm BST

LONDON, May 12, 2022 (GLOBE NEWSWIRE) -- Autolus Therapeutics plc(Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, today announces the online publication of four abstracts submitted to the European Hematology Association (EHA) Congress to be held June 9-12, 2022. Autolus plans to present more detail on these programs and the next steps in a conference call following the EHA presentations, on June 13, 2022, details below.

We are delighted to be presenting encouraging early clinical data from four of our pipeline programs, including important additive safety and efficacy data from our lead asset obe-cel in indications beyond adult r/r B-ALL. These data demonstrate the inherent value in both our pipeline and our technology base from which it originates, said Dr. Christian Itin, Chief Executive Officer of Autolus. With oral presentations on the early safety, tolerability, feasibility and preliminary efficacy of AUTO4 and AUTO1/22, were in a great place to evaluate the next strategic steps for these candidates and further build on the data presented here.

Abstracts to be presented:

Conference Call

Management will host a conference call and webcast on June 13, 2022 at7:30 am ET/12:30 pm BST to discuss the EHA data. To listen to the webcast and view the accompanying slide presentation, please go to the events section of Autolus website.

The call may also be accessed by dialing (866) 679-5407 for U.S. and Canada callers or (409) 217-8320 for international callers. Please reference conference ID: 6594553. After the conference call, a replay will be available for one week. To access the replay, please dial (855) 859-2056 for U.S. and Canada callers or (404) 537-3406 for international callers. Please reference conference ID: 6594553.

About Autolus Therapeutics plcAutolus is a clinical-stage biopharmaceutical company developing next-generation, programmed T cell therapies for the treatment of cancer. Using a broad suite of proprietary and modular T cell programming technologies, the Company is engineering precisely targeted, controlled and highly active T cell therapies that are designed to better recognize cancer cells, break down their defense mechanisms and eliminate these cells. Autolus has a pipeline of product candidates in development for the treatment of hematological malignancies and solid tumors. For more information, please visit http://www.autolus.com.

About obe-cel(AUTO1)Obe-cel is a CD19 CAR T cell investigational therapy designed to overcome the limitations in clinical activity and safety compared to current CD19 CAR T cell therapies.Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T cells, obe-cel may reduce toxicity and be less prone to T cell exhaustion, which could enhance persistence and improve the ability of the programmed T cells to engage in serial killing of target cancer cells. In collaboration with Autolus academic partner, UCL, obe-cel is currently being evaluated in a Phase 1 clinical trials for B-NHL. Autolus has progressed obe-cel to the FELIX trial, a potential pivotal trial for adult ALL.

About obe-cel FELIX clinical trialAutolus Phase 1b/2 clinical trial of obe-cel is enrolling adult patients with relapsed / refractory B-precursor ALL. The trial had a Phase 1b component prior to proceeding to the single arm, Phase 2 clinical trial. The primary endpoint is overall response rate, and the secondary endpoints include duration of response, MRD negative CR rate and safety. The trial is designed to enroll approximately 100 patients across 30 of the leading academic and non-academic centers in the United States,United KingdomandEurope. [NCT04404660]

About AUTO1/22AUTO1/22 is a novel dual targeting CAR T cell based therapy candidate based on obe-cel. It is designed to combine the enhanced safety, robust expansion & persistence seen with the fast off rate CD19 CAR from obe-cel with a high sensitivity CD22 CAR to reduce antigen negative relapses. This product candidate is currently in a Phase 1 clinical trial called CARPALL for patients with r/r pediatric ALL. [NCT02443831]

About AUTO4AUTO4 is a programmed T cell product candidate in clinical development for T cell lymphoma, a setting where there are currently no approved programmed T cell therapies. AUTO4 is specifically designed to target TRBC1 derived cancers, which account for approximately 40% of T cell lymphomas, and is a complement to the AUTO5 T cell product candidate, which is in pre-clinical development. AUTO4 has been tested in a Phase 1 clinical trial, LibRA1 for patients with peripheral T cell Lymphoma.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as "may," "will," "could," "expects," "plans," "anticipates," and "believes." These statements include, but are not limited to, statements regarding Autolus development of the obe-cel program; the future clinical development, efficacy, safety and therapeutic potential of its product candidates, including progress, expectations as to the reporting of data, conduct and timing and potential future clinical activity and milestones; expectations regarding the initiation, design and reporting of data from clinical trials; expectations regarding regulatory approval process for any product candidates; the collaboration between Autolus and Blackstone; the discovery, development and potential commercialization of potential product candidates including obe-cel using Autolus technology and under the collaboration agreement; the therapeutic potential for Autolus in next generation product developments of obe-cel in B-cell malignancies; the potential and timing to receive milestone payments and pay royalties under the strategic collaboration; and the Companys anticipated cash runway. Any forward-looking statements are based on management's current views and assumptions and involve risks and uncertainties that could cause actual results, performance, or events to differ materially from those expressed or implied in such statements. These risks and uncertainties include, but are not limited to, the risks that Autolus preclinical or clinical programs do not advance or result in approved products on a timely or cost effective basis or at all; the results of early clinical trials are not always being predictive of future results; the cost, timing and results of clinical trials; that many product candidates do not become approved drugs on a timely or cost effective basis or at all; the ability to enroll patients in clinical trials; possible safety and efficacy concerns; and the impact of the ongoing COVID-19 pandemic on Autolus business. For a discussion of other risks and uncertainties, and other important factors, any of which could cause Autolus actual results to differ from those contained in the forward-looking statements, see the section titled "Risk Factors" in Autolus' Annual Report on Form 20-F filed with the Securities and Exchange Commission on March 10, 2022, as well as discussions of potential risks, uncertainties, and other important factors in Autolus' subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Autolus undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required by law.

Contact:

Olivia Manser+44 (0) 7780 471568o.manser@autolus.com

Julia Wilson+44 (0) 7818 430877j.wilson@autolus.com

Susan A. NoonanS.A. Noonan Communications+1-917-513-5303susan@sanoonan.com

Lasers, Fish-Skin Bandages and Pain-Free Vaccines: The Winners of Our 3rd Annual STEM Writing Contest – The New York Times

Saahil Joshi, age 17, Crystal Springs Uplands School, Hillsborough, Calif.: Too Many Cooks Spoil the Broth: The Science and Future of Drug-Drug Interactions

Micah: Salt: The Sapid and Sophisticated Seasoning

Katherine Kricorian, age 17, Santa Susana High School, Simi Valley, Calif.: From Algae to Energy: A Blooming Solution to Pollution

Chloe Lee, age 14, Korea International School Pangyo Campus, Gyeonggi-do, Korea: Do Plants Have Feelings?

Seungjae (Andy) Lee, age 13, Hong Kong International School, Tai Tam, Hong Kong: Keeping Your Pet Friend Forever: Is Cloning a Soul Possible?

Zhuocheng Li, age 16, Green Hope High School, Cary, N.C.: The Blood That Saved Countless Lives

Andrew C. Lin, age 12, Visions in Education Homeschool Academy, Carmichael, Calif.: Breaking the Speech Barrier

Andy Lu, age 16, Desert Vista High School, Phoenix: Hypersonic Flight: Can We Go Faster?

Camille: Sugar and the Body: A Bittersweet Relationship

Natalia Meza, age 17, American School of Madrid, Madrid: What Happens in Vagus, Stays in Vagus?

Aman Mistry, age 17, Smithtown High School, East Saint James, N.Y.: Helping a Blind Man See: The Miracle of Optogenetics

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Lasers, Fish-Skin Bandages and Pain-Free Vaccines: The Winners of Our 3rd Annual STEM Writing Contest - The New York Times

Google Reverses Ban on Ads for All Stem Cell Therapies, Will Allow FDA-Approved Ones – Gizmodo

Photo: Scott Strazzante/San Francisco Chronicle (AP)

Google announced Monday it will allow ads for stem cell treatments approved by the Food and Drug Administration to appear in search results starting in July. The tech giant previously banned any ads for stem cell therapies, FDA-approved or otherwise.

In an update to its policies page first spotted by Gizmodo, the company said that, starting July 11, it will permit search engine ads for stem cell therapies given the thumbs up from the FDA, a very small list of just 23 companies that treat some blood disorders and cancers, according to the FDAs website.

At the same time, Google is clarifying its policy language on stem cell therapy ads, which would allow a global cell or gene therapy company to advertise if the ads are are exclusively educational or informational in nature, regardless of regulatory approval status. Google did not clarify what would constitute educational or informational, nor did the company respond to a request for comment how it will restrict less-than-reputable products from being advertised with its technology going forward. We will update the story if we hear more.

The search engine said it banned all advertising for stem cell treatments back in 2019, proclaiming at the time it was restricting ads that have no established biomedical or scientific basis. In 2021, the company clarified that it was restricting ads for experimental treatments meant for so-called biohacking or other DIY genetic engineering, as well as any cell or gene therapies like stem cell therapy.

Despite the pledge to ban such ads or Mondays announced change, a simple Google search reveals just how easily bad actors can get around the restrictions. Searching for stem cells for neuropathy reveals several misleading ad results for stem cell treatments that are not FDA approved, though at least one maker claims it is FDA registered and another says its treatment is supported by FDA master files.

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Paul Knoepfler, a professor at the University of California Davis School of Medicine who researches stem cells and cancer, has written before about Googles problematic search engine ad policies that allow stem cell companies to easily advertise their products in spite of the tech giants rules. In an email, he told Gizmodo he is concerned How effectively the new rule for strictly educational ads would be maintained, particularly given the context of Google Search now so often highly ranking promotional clinic websites arguably presented as educational material.

Stem cells as an industry have grown rapidly in recent years and are expected to continue doing so, with MarketWatch reporting in February the $2.75 billion industry is expected to more than double to $5.72 billion by 2028.

Stem cell treatments are approved by the FDAs Cellular, Tissue and Gene Therapies Advisory Committee. Though some companies claim in advertising they have FDA approval, being listed on clinicaltrials.gov database or being registered with the FDA isnt full-on approval, according to the agencys guidelines. The fact that companies regularly run around Googles existing policies leaves even more questions on the table. Knoepfler asked whether clinical trial recruitment be allowed, when hes often seen such trials already claiming their treatment already works.

Perhaps good citizens in the regenerative medicine world want the opportunity to run such ads related to clinical trial recruitment, but even exclusively educational ads of that type with good intentions could run into ethical issues, Knoepfler added.

Shoshana Wodinsky contributed reporting.

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Google Reverses Ban on Ads for All Stem Cell Therapies, Will Allow FDA-Approved Ones - Gizmodo

Autolus Therapeutics to Present Four Clinical Data Updates at the European Hematology Association Congress – Yahoo Finance

Autolus Limited

LONDON, May 12, 2022 (GLOBE NEWSWIRE) -- Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, today announces the online publication of four abstracts submitted to the European Hematology Association (EHA) Congress to be held June 9-12, 2022. Autolus plans to present more detail on these programs and the next steps in a conference call following the EHA presentations, on June 13, 2022, details below.

Abstracts to be presented:

Title: Safety and preliminary efficacy findings of AUTO4, a TRBC1-targetting CAR, in relapsed/refractory TRBC1 positive selected T Cell Non-Hodgkin Lymphoma LINKSession Title: Gene therapy and cellular immunotherapy - Clinical 2Session date and time: Saturday, June 11 - 16:30 - 17:45 CESTSession room: Hall Strauss 1-2Final Abstract Code: S261Presenting Author: Kate CwynarskiSummary: Peripheral T cell lymphomas (PTCL) are typically aggressive, treatment resistant, and associated with poor prognosis. Finding the right target is challenging because there is a lack of tumor-specific antigens, and pan-T cell depletion leads to immunosuppression. T cell lymphoma is clonal, and tumor cells express either TRBC1 or TRBC2. AUTO4 targets TRBC1+ cells, which allows part of the T cell compartment to be retained. As of 9 February 2022, 9 patients screened for r/r TRBC1+ peripheral T-cell lymphoma have been treated with AUTO4. Two patients had prior stem cell transplantation. After lymphodepletion with Flu/Cy, 3 patients received 25 x 106 CAR T cells, 2 patients received 75 x 106 CAR T cells, 1 patient received 225 x 106 CAR T cells and 3 patients received 450 x 106 CAR T cells. AUTO4 demonstrated a tolerable safety profile, with no patient experiencing any dose limiting toxicities, and no neurotoxicity/immune effector cell-associated neurotoxicity (ICANS). Three patients experienced cytokine release syndrome (CRS) (1 patient with Grade 1, 1 patient with Grade 2 and 1 patient with Grade 3). Of the 9 patients treated, 5 patients had achieved complete metabolic responses (CMR) by PET-CT at Month 1, 1 patient remains with a partial response (PR) 6 months post AUTO4 infusion, and 3 patients did not respond. All 3 patients at the highest dose level achieved a CMR at Month 1.

Title: Dual antigen targeting with co-transduced CD19/22 CAR T cells for relapsed/refractory ALL (AUTO1/22) LINKSession Title: Gene therapy and cellular immunotherapy - Clinical 1Session date and time: Saturday, June 11 - 11:30 - 12:45 CESTSession room: Hall Strauss 1-2Final Abstract Code: S259Presenting Author: Sara GhorashianSummary: CD19 negative escape is a major cause of relapse after CD19 CAR T cell therapy for relapsed/refractory (r/r) pediatric ALL. To overcome this challenge, AUTO1/22 builds on the favorable safety profile and excellent persistence of obe-cel by combining it with an additional CD22 targeting CAR. As of 8 February 2022, 10 pediatric ALL patients have been treated with AUTO1/22 and 8 are evaluable with >1 month follow-up. 5 of 8 patients had relapsed post allogeneic stem cell transplant (SCT), 4 had received prior Blincyto and 3 had relapsed after prior Kymriah. CRS occurred in 7/8 patients (grade 1 n=2, grade 2 n=5), but severe CRS was not seen. 7 of 8 evaluable patients achieved MRD negative complete response (CR) at 1 month post infusion. Overall, at a median follow up of 4.8 months, 5/8 patients remain in MRD negative CR at last follow up. The study results demonstrate that dual CD19/22 targeting CAR T cells generated by co-transduction show an acceptable safety profile, with robust expansion/persistence and early efficacy in a heavily pre-treated cohort. To date with limited follow-up we have not observed antigen negative relapse but longer follow up is needed.

Title: Safety and efficacy findings of AUTO1, a fast off-rate CD19 CAR, in relapsed/refractory Primary CNS Lymphoma LINKSession Title: Poster sessionSession date and time: Friday, June 10 - 16:30 - 17:45 CESTFinal Abstract Code: P1460Presenting Author: Claire RoddieSummary: Relapsed/refractory primary central nervous system lymphoma (PCNSL) has a median overall survival of 2-8 months and few therapeutic options. obe-cel (AUTO1) has previously demonstrated high remission rates, low incidence of CRS/ICANS and long-term persistence, making it a viable treatment option for PCNSL. As of 14 February 2022, the CAROUSEL study enrolled 6 patients with r/r PCNSL where the median prior lines of treatment was 2. 5 patients were infused with IV AUTO1 and 1 patient with intraventricular AUTO1. Following CAR T infusion, Grade 1 and 2 CRS affected 1 and 3 patients respectively and any Grade ICANS was observed in 2 patients with 2 Grade 3 events. AUTO1 engraftment and response was evaluable in 4 patients at 1 month following iv infusion. 2 of 4 patients had no measurable disease at 2 and 6 months of follow up respectively. AUTO1 showed encouraging remission rates and excellent CAR T engraftment/expansion in the blood and CSF. Intraventricular administration was well-tolerated and showed that AUTO1 has activity via that route in a patient who failed IV therapy. Additional patients updated biological data and longer follow up will be presented.

Title: Safety and efficacy findings of AUTO1, a fast off-rate CD19 CAR, in relapsed/refractory B-Cell Non-Hodgkins Lymphoma (B-NHL), and chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL) LINKSession Title: Poster sessionSession date and time: Friday, June 10 - 16:30 - 17:45 CESTFinal Abstract Code: P1459Presenting Author: Claire Roddie Summary: obe-cel (AUTO1) has demonstrated an excellent safety profile in previous trials, with low levels of CRS/ICANS and long-term engraftment of CAR T cells, making it an ideal CAR T candidate to evaluate in B-NHL, CLL/SLL. As of 8 February 2022, 19 patients had been infused with AUTO1; 10 with low grade NHL, 6 with DLBCL and 3 with CLL. Patients treated had received a median of 3 prior lines of treatment. Grade 1 CRS was reported in 6/19 and Grade 2 CRS in 3/19. No ICANS was observed in the B-NHL and CLL cohorts. In the lg-NHL and DCBCL cohorts, 10/10 and 4/5 evaluable patients respectively were in CMR post-treatment. Responses were ongoing in 9/10 lg-NHL at 12 months and in 4/4 DLBCL at months 1,3,3 and 6. In the CLL cohort, 2/3 evaluable patients achieved MRD negative remission in the bone marrow with residual small volume lymph nodes by CT at 6 and 3 months of follow up respectively. AUTO1 demonstrated a tolerable safety profile in patients with r/r B-NHL and CLL despite high disease burden. Early data shows excellent complete remission rates and CAR engraftment/expansion. Additional patients, updated data and longer follow up will be presented.

Story continues

Conference Call

Management will host a conference call and webcast on June 13, 2022 at 7:30 am ET/12:30 pm BST to discuss the EHA data. To listen to the webcast and view the accompanying slide presentation, please go to the events section of Autolus website.

About obe-cel (AUTO1)Obe-cel is a CD19 CAR T cell investigational therapy designed to overcome the limitations in clinical activity and safety compared to current CD19 CAR T cell therapies. Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T cells, obe-cel may reduce toxicity and be less prone to T cell exhaustion, which could enhance persistence and improve the ability of the programmed T cells to engage in serial killing of target cancer cells. In collaboration with Autolus academic partner, UCL, obe-cel is currently being evaluated in a Phase 1 clinical trials for B-NHL. Autolus has progressed obe-cel to the FELIX trial, a potential pivotal trial for adult ALL.

Contact:

Olivia Manser+44 (0) 7780 471568o.manser@autolus.com

Julia Wilson+44 (0) 7818 430877j.wilson@autolus.com

Susan A. NoonanS.A. Noonan Communications+1-917-513-5303susan@sanoonan.com

Originally posted here:
Autolus Therapeutics to Present Four Clinical Data Updates at the European Hematology Association Congress - Yahoo Finance

Gracell Biotechnologies to Present Clinical Data on BCMA/CD19 Dual-targeting CAR-T GC012F in RRMM and B-NHL and CD19/CD7 Dual-directed Allogeneic…

SAN DIEGO, Calif., SUZHOU and SHANGHAI, China , May 12, 2022 /PRNewswire/ -- Gracell Biotechnologies Inc. ("Gracell" or the "Company",NASDAQ: GRCL), a global clinical-stage biopharmaceutical company dedicated to developing highly efficacious and affordable cell therapies for the treatment of cancer, today announced the details of three abstracts that it will present at the European Hematology Association 2022 Hybrid Congress (EHA2022 Congress), being held from June 9 June 12 in Vienna, Austria. The abstracts highlight the clinical data from ongoing investigator-initiated trials (IITs) of BCMA/CD19 dual-targeting FasTCAR candidate GC012F in two indications of B-cell non-hodgkin's lymphoma (B-NHL) and relapsed/refractory multiple myeloma (RRMM), and allogeneic TruUCAR candidate GC502 in B-cell acute lymphoblastic leukemia (B-ALL).

"We are very excited to share our data for both our FasTCAR candidate GC012F in two indications of RRMM and B-NHL, and allogeneic TruUCAR candidate GC502 in B-ALL at the EHA2022 Congress," said Dr. Martina Sersch, Chief Medical Officer of Gracell. "The new data, including the expanded indication of GC012F into B-NHL, demonstrates the potential of our platforms and provides further validation. The clinical data of BCMA/CD19 dual-targeting GC012F in the treatment of B-NHL shows promising early results, along with benefits of the next-day manufacturing enabled by the FasTCAR platform. The CD19/CD7 dual-directed CAR-T therapy GC502 is our second allogeneic candidate on our TruUCAR platform, demonstrating the potential wide applicability of the TruUCAR design."

BCMA/CD19 Dual-Targeting FasTCAR-T GC012F for the Treatment of B-NHL

GC012F is an autologous CAR-T therapeutic candidate dual-targeting B cell maturation antigen (BCMA) and CD19. It is developed using Gracell's proprietary FasTCAR platform which enables next-day manufacturing, and is currently being evaluated in IITs in China including in RRMM and B-NHL. GC012F is the first BCMA/CD19 dual-targeting CAR-T in human trials for B-NHL.

Gracell will present the early results of the first-in-human phase 1 IIT in China evaluating the safety and tolerability of GC012F in B-NHL patients. Three patients who had received a median of two prior lines of therapy were enrolled, all of which presented with bulky disease. As of the February 22, 2022 data cutoff date, the enrolled patients had received one single infusion of GC012F at three different doses of 3.7x104 cells/kg and 2-3x105 cells/kg.

All three patients had achieved a complete response (CR) confirmed by PET- CT at day 28 after GC012F infusion. At 3-month follow-up, both of the two assessable patients had ongoing response. No dose-limiting toxicities were observed and no immune effector cell-associated neurotoxicity syndrome (ICANS) were observed. CRS presented as Grade 1 in two patients and Grade 3 in one patient (duration of two days) with no Grade 4 or 5 events.

Details of the presentation are as follows:

BCMA/CD19 Dual-Targeting FasTCAR-T GC012F for the Treatment of RRMM

Gracell will also present as an oral abstract presentation the updated results from the first-in-human IIT evaluating GC012F for the treatment of RRMM patients. This data is currently under embargo and will be published on the EHA2022 Hybrid Congress website on Thursday, May 26 concurrently with ASCO.

Details of the presentation are as follows:

CD19/CD7 Dual-directed Allogeneic TruUCAR-T GC502 for the Treatment of B-ALL

GC502 leverages the novel dual-directed CAR design of Gracell's proprietary TruUCAR platform, designed to generate high-quality allogeneic CAR-T cell therapies that can be administered "off-the-shelf" at lower cost and with faster patient's access. TruUCAR-enabled GC502 utilizes the dual-directed CAR design with one CAR targeting CD19 on malignant cells and a second CAR targeting CD7 to suppress host-versus-graft rejection. An enhancer molecule is embedded in the basic construct of TruUCAR to enhance proliferation of TruUCAR T cells.

Between September 2021 and January 2022, four r/r B-ALL patients were enrolled and treated in an open-label, non-randomized, prospective IIT in China in two different dose levels and with two different formulations. Patients were heavily pretreated, and all had previously received either autologous or donor derived CD19 or CD19/CD22 targeted CAR-T therapy. As of the January 28, 2022 data cutoff date, all four patients had received a single dose of GC502, including one patient at dose level 1 (DL1) 1.0x107 cells/kg and three patients at dose level 2 (DL2) 1.5x107 cells/kg. Patients received a Flu/Cy based lymphodepletion regimen prior to treatment with GC502.

Three of four patients achieved minimal residual disease negative complete response or complete response with incomplete count recovery (MRD- CR/CRi), and one patient achieved a partial response at month one and subsequently received allogeneic hematopoietic stem-cell transplantation (allo-HSCT) on day 39.

Cytokine release syndrome (CRS) presented as Grade 2 and Grade 3 with no Grade 4 or 5 events. No immune effector cell-associated neurotoxicity syndrome (ICANS) or acute graft-versus-host disease (aGvHD) were observed.

Details of the presentation are as follows:

For more information about the EHA2022 Hybrid Congress, visit http://www.ehaweb.org.

About GC012F

GC012F is a FasTCAR-enabled dual-targeting CAR-T product candidate that is currently being evaluated in IIT studies in China for the treatment of multiple myeloma and B-cell non-Hodgkin's lymphoma. GC012F simultaneously targets CD19 and BCMA to drive fast, deep and durable responses, which can potentially improve efficacy and reduce relapse in multiple myeloma and B-NHL patients.

About B-NHL

Non-Hodgkin's lymphoma (NHL) is a group of blood cancers that developed from lymphocytes, most commonly derived from B cells (B-NHL). Globally, approximately 510,000 patients are diagnosed with NHL every year with about 80,470 patients expected to be diagnosed with NHL in the United States in 2022[1]. B-NHL accounts for approximately 85% of NHL diagnoses.

[1] Data source: American Cancer Society

About GC502

GC502 is a TruUCAR-enabled CD19/CD7 dual-directed, off-the-shelf allogeneic CAR-T product candidate that is being studied in an ongoing Phase 1 IIT in China for the treatment of B-cell malignancies. GC502 is manufactured using T cells from non-human leukocyte antigen (HLA) matched healthy donors. An enhancer molecule is embedded in the basic construct of TruUCAR to enhance proliferation of TruUCAR T cells. Optimized for CD19/CD7 dual-CAR functionality and in vivo durability, GC502 has demonstrated robust anti-tumor effects with potential to suppress host versus graft (HvG) rejection in preclinical models.

About B-ALL

Acute lymphoblastic leukemia (ALL) is a type of blood cancer characterized by proliferation of immature lymphocytes in the bone marrow, which can involve either T lymphocytes (T-ALL), or B lymphocytes (B-ALL). Globally, approximately 64,000 patients are diagnosed with ALL every year with an estimated 6,660 new cases to be diagnosed in the United States in 2022[2]. B-ALL accounts for 75% of ALL diagnoses in adults.

[2] Data source: American Cancer Society

About FasTCAR

CAR-T cells manufactured on Gracell's proprietary FasTCAR platform appear younger, less exhausted and show enhanced proliferation, persistence, bone marrow migration and tumor cell clearance activities as demonstrated in preclinical studies. With next day manufacturing, FasTCAR is able to significantly improve cell production efficiency which may result in meaningful cost savings, and, together with fast turnaround time, enables enhanced accessibility of cell therapies for cancer patients.

About TruUCAR

TruUCAR is Gracell's proprietary technology platform and is designed to generate CAR-T cell therapies from high quality allogeneic T cells that can be administered "off-the-shelf" at lower cost and with improved accessibility of cell therapies for cancer patients. With differentiated design enabled by gene editing, TruUCAR is designed to control HvG as well as GvHD without the need for being co-administered with additional strong immunosuppressant after conventional lymphodepletion. The novel dual-CAR design allows tumor antigen-CAR moiety to target malignant cells, while the CD7 CAR moiety is designed to suppress rejection (HvG response) of allogeneic CAR-T cells by host T and NK cells (HvG).

About Gracell

Gracell Biotechnologies Inc.("Gracell") is a global clinical-stage biopharmaceutical company dedicated to discovering and developing breakthrough cell therapies. Leveraging its pioneering FasTCAR and TruUCAR technology platforms and SMART CARTMtechnology module, Gracell is developing a rich clinical-stage pipeline of multiple autologous and allogeneic product candidates with the potential to overcome major industry challenges that persist with conventional CAR-T therapies, including lengthy manufacturing time, suboptimal cell quality, high therapy cost, and lack of effective CAR-T therapies for solid tumors. For more information on Gracell, please visit http://www.gracellbio.com.Follow @GracellBio on LinkedIn.

Cautionary Noted Regarding Forward-Looking Statements

Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward-looking statements" within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to the expected trading commencement and closing date of the offering. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including factors discussed in the section entitled "Risk Factors" in Gracell's most recent annual report on Form 20-F as well as discussions of potential risks, uncertainties, and other important factors in Gracell's subsequent filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Gracell specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. Readers should not rely upon the information on this page as current or accurate after its publication date.

Media contacts

Marvin Tang[emailprotected]

Kyle Evans[emailprotected]

Investor contacts

Gracie Tong[emailprotected]

Stephanie Carrington[emailprotected]

SOURCE Gracell Biotechnologies Inc.

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