Monthly Archives: April 2022

Oral Cavity | histology – University of Michigan

Posted: April 19, 2022 at 1:52 am

1. Lining Mucosa

Slide 114R (lip, human, H&E) View Virtual Slide Slide 114 triC (lip, human, trichrome) View Virtual SlideSlide 114M (lip, monkey, H&E) View Virtual Slide

A stratified squamous non-keratinized epithelium lines the oral surface of the lips, cheeks, floor of mouth, and covers the ventral surface of the tongue In slide 114 (human) and 114M (monkey) of the lip, note that skin (stratified, keratinized squamous epithelium with hair follicles) covers the external surface View Image, skeletal muscle (orbicularis oris muscle) forms the core View Image, and a mucosal epithelium(stratified, non-keratinizing squamous epithelium) covers the internal surface View Image. A lamina propria underlies the mucosa and small salivary glands (labial salivary glands) View Image are present in the submucosa. Note the transition zone between the keratinized epithelium of the skin and the nonkeratinized epithelium of the mucosa. This transition zone is called the vermillion zone(present only in humans) View Image. In the transition zone, long connective tissue papillae extend deep into the epithelium. Capillaries are carried close to the surface in these papillae. Because the epithelium is very thin in this region, the lips appear red (this arrangement may or may not be apparent in your glass slides). Salivary glands are lacking in the vermillion zone, therefore, the lips must be continuously moistened (by the tongue) to prevent drying out.

Slide 115 (fetal palate, H&E) View Virtual SlideSlide 115 (fetal palate, trichrome) View Virtual Slide

A stratified squamous keratinized epithelium is found on surfaces subject to the abrasion that occurs with mastication, e.g., the roof of the mouth (palate) and gums (gingiva). Slide 115, which you used to study bone and the respiratory system, is a longitudinal section through the palate and includes the lip, gingiva, hard palate, and a portion of the soft palate [orientation]. This tissue is from a term fetus (with unerrupted teeth) and the epithelium over the hard palate is not yet fully differentiated (i.e. not fully keratinized). The slide is, however, a good overall orientation to the histology of the hard and soft palate. In the adult the epithelium of the hard palate is keratinized. Identify respiratory epithelium, bone (hard palate), forming tooth View Image, and skeletal muscle in the lipView Image and the soft palate View Image. Some slides show mucous salivary glands View Image in the submucosa.

Slide 116 40x (tongue, H&E) View Virtual SlideSlide 117 20x (tongue, H&E) View Virtual SlideSlide 117 40x (tongue, H&E) View Virtual SlideSlide 117N 40x (tongue, rabbit, H&E) View Virtual Slide

The dorsal surface and lateral borders of the tongue are covered by a mucous membrane that contains nerve endings for general sensory reception and taste perception. In slide 116, the dorsal surface of the tongue is covered with tiny projections called papillae View Image, which are lacking on the ventral surface. The body of the tongue is composed of interlacing bundles of skeletal muscle View Image that cross one another at right angles. The dense lamina propria of the mucosa is continuous with the connective tissue of the muscle, tightly binding the mucous membrane to the muscle. Some glass slides in our collection show mucous glands in the submucosa, which are found only on the ventral side of the tongue. These glands are not present in the digital slides, but their ducts may be seen View Image.

In slide 116 there are two types of papillae on the tongue. Locate the numerous filiform papillae View Image, that appear as conical structures with a core of lamina propria covered by a keratinized epithelium. Fungiform papillae View Image are scattered among the filiform papillae. They have expanded smooth round tops and narrower bases. In young children, the fungiform papillae can be seen with the naked eye as red spots on the dorsum of the tongue (because the non-keratinized epithelium is relatively translucent). These papillae are less readily observed in adults, because of slight keratinization of the epithelium.

Slide 117 and especially slide 117N contain examples of circumvallate papillaeView Image. These are large circular papillae surrounded by a deep trench. The covering epithelium is non-keratinized. Taste budsView Image, the chemoreceptors for the sense of taste, are located on the lateral borders. Each taste bud contains about 50 spindle shaped cells that are classically described based on their appearance as light (receptor) cells, dark (supporting) cells, and basal (stem) cells, although these distinctions are difficult to see in your slides so we do not require you to identify the cell types. Non-myelinated nerves from cranial nerves VII, IX, or X (depending on the location of the taste bud) synapse with the receptor and, to some extent, supporting cells of the taste bud. Some slides show serous glands (of von Ebner) View Image in the lamina propria and interspersed between the bundles of muscle beneath the papillae. These glands drain into the base of the trench around the circumvallate papillae.

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Oral Cavity | histology - University of Michigan

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Unraveling Stem Cells’ Secrets: Immortality of Germline Cells and the Function of Junk DNA – SciTechDaily

Posted: April 19, 2022 at 1:52 am

MIT biology professor Yukiko Yamashita has spent much of her career exploring how asymmetrical cell divisions occur. This type of cell division allows cells to differentiate into different types of tissue, and also helps germline cells such as eggs and sperm to maintain their viability from generation to generation. Credit: M. Scott Brauer

The MIT biologist Yukiko Yamashitas research has shed light on the immortality of germline cells and the function of junk DNA.

When cells divide, they usually generate two identical daughter cells. However, there are some important exceptions to this rule: When stem cells divide, they often produce one differentiated cell along with another stem cell, to maintain the pool of stem cells.

Yukiko Yamashita has spent much of her career exploring how these asymmetrical cell divisions occur. These processes are critically important not only for cells to develop into different types of tissue, but also for germline cells such as eggs and sperm to maintain their viability from generation to generation.

We came from our parents germ cells, who used to be also single cells who came from the germ cells of their parents, who used to be single cells that came from their parents, and so on. That means our existence can be tracked through the history of multicellular life, Yamashita says. How germ cells manage to not go extinct, while our somatic cells cannot last that long, is a fascinating question.

Yamashita, who began her faculty career at the University of Michigan, joined MIT and the Whitehead Institute in 2020, as the inaugural holder of the Susan Lindquist Chair for Women in Science and a professor in the Department of Biology. She was drawn to MIT, she says, by the eagerness to explore new ideas that she found among other scientists.

When I visited MIT, I really enjoyed talking to people here, she says. They are very curious, and they are very open to unconventional ideas. I realized I would have a lot of fun if I came here.

By studying fruit flies, Yukiko Yamashita has discovered the function of DNA segments that were previously thought to be junk. Credit: MIT

Before she even knew what a scientist was, Yamashita knew that she wanted to be one.

My father was an admirer of Albert Einstein, so because of that, I grew up thinking that the pursuit of the truth is the best thing you could do with your life, she recalls. At the age of 2 or 3, I didnt know there was such a thing as a professor, or such a thing as a scientist, but I thought doing science was probably the coolest thing I could do.

Yamashita majored in biology at Kyoto University and then stayed to pursue her PhD, studying how cells make exact copies of themselves when they divide. As a postdoc at Stanford University, she became interested in the exceptions to that carefully orchestrated process, and began to study how cells undergo divisions that produce daughter cells that are not identical. This kind of asymmetric division is critical for multicellular organisms, which begin life as a single cell that eventually differentiates into many types of tissue.

Those studies led to a discovery that helped to overturn previous theories about the role of so-called junk DNA. These sequences, which make up most of the genome, were thought to be essentially useless because they dont code for any proteins. To Yamashita, it seemed paradoxical that cells would carry so much DNA that wasnt serving any purpose.

I couldnt really believe that huge amount of our DNA is junk, because every time a cell divides, it still has the burden of replicating that junk, she says. So, my lab started studying the function of that junk, and then we realized it is a really important part of the chromosome.

When I visited MIT, I really enjoyed talking to people here, Yamashita says. They are very curious, and they are very open to unconventional ideas. I realized I would have a lot of fun if I came here. Credit: M. Scott Brauer

In human cells, the genome is stored on 23 pairs of chromosomes. Keeping all of those chromosomes together is critical to cells ability to copy genes when they are needed. Over several years, Yamashita and her colleagues at the University of Michigan, and then at MIT, discovered that stretches of junk DNA act like bar codes, labeling each chromosome and helping them bind to proteins that bundle chromosomes together within the cell nucleus.

Without those barcodes, chromosomes scatter and start to leak out of the cells nucleus. Another intriguing observation regarding these stretches of junk DNA was that they have much greater variability between different species than protein-coding regions of DNA. By crossing two different species of fruit flies, Yamashita showed that in cells of the hybrid offspring flies, chromosomes leak out just as they would if they lost their barcodes, suggesting that the codes are specific to each species.

We think that might be one of the big reasons why different species become incompatible, because they dont have the right information to bundle all of their chromosomes together into one place, Yamashita says.

Yamashitas interest in stem cells also led her to study how germline cells (the cells that give rise to eggs and sperm cells) maintain their viability so much longer than regular body cells across generations. In typical animal cells, one factor that contributes to age-related decline is loss of genetic sequences that encode genes that cells use continuously, such as genes for ribosomal RNAs.

A typical human cell may have hundreds of copies of these critical genes, but as cells age, they lose some of them. For germline cells, this can be detrimental because if the numbers get too low, the cells can no longer form viable daughter cells.

Yamashita and her colleagues found that germline cells overcome this by tearing sections of DNA out of one daughter cell during cell division and transferring them to the other daughter cell. That way, one daughter cell has the full complement of those genes restored, while the other cell is sacrificed.

That wasteful strategy would likely be too extravagant to work for all cells in the body, but for the small population of germline cells, the tradeoff is worthwhile, Yamashita says.

If skin cells did that kind of thing, where every time you make one cell, you are essentially trashing the other one, you couldnt afford it. You would be wasting too many resources, she says. Germ cells are not critical for viability of an organism. You have the luxury to put many resources into them but then let only half of the cells recover.

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Scientists De-Aged a Woman’s Skin Cells by 30 Years – The Daily Beast

Posted: April 19, 2022 at 1:52 am

While the Fountain of Youth is the stuff of legend, the search for a way to stop humans from aging is happening as we speakinside the laboratory.

In a study published in the journal eLife on April 8, scientists at Babraham Institute in the U.K. managed to de-age the skin cells of a 53-year-old woman by 30 years in a petri dish. Looking at age-related biological changes in the DNA, these genetically-modified younger cells appeared and behaved as any 23-year-old skin cell should. Notably, the team was also able to de-age the cells in less than two weeks.

The techniques used in this experiment have been around for the last few decades. However, with the woman's skin cells, the researchers managed to shave off time from the usually long process while also avoiding the problems reprogrammed cells can often run into, like inadvertently turning cancerous.

This kind of work is very important, Dr. Ivona Percec, a plastic surgeon and stem cell researcher at the University of Pennsylvania School of Medicine, who was not involved in the study, told The Daily Beast. And its one thats been sought out by many scientists in order to reverse or delay aging.

Most rejuvenation or regeneration research makes use of human stem cells, which have the unique ability to develop into any other type of cell our body needs, such as muscle and brain cells. Stem cells can also renew themselves over time and serve as an internal repair system, replacing lost or damaged cells during a persons lifetime. But stem cells are quite difficult to produce in the laband are often rejected by the body when used in different types of therapies.

To get around these hurdles, scientists have been creating their own lab-grown stem cells called induced pluripotent stem cells (iPSCs). They are created by taking any cell in our body and genetically editing it to resemble an embryonic stem cell, George Sen, a molecular biologist at the University of California San Diego who was not involved in the study, told The Daily Beast in an email.

To make their iPSCs, the Babraham researchers reversed the cellular clock on their 53-year-old skin cells by bathing them in a chemical solution that encourages the growth of proteins that reshape a cells DNA. To control how far they de-age the cells, the researchers allowed the bath to run for a little less than two weeks than the typical 50 days. Then they assessed the age of the skin cells by looking for age-related biological changes.

I remember the day I got the results back and I didn't quite believe that some of the cells were 30 years younger than they were supposed to be, Dilgeet Gill, a biomedical researcher at Babraham Institute and lead author of the study, told the BBC. It was a very exciting day!"

Young fibroblasts in the first image. The next two images are after 10 days, right with treatment. The last two images are after 13 days, right with treatment. Red shows collagen production which has been restored.

Ftima Santos

These newly minted young skin cells, called fibroblasts, produce collagen, which is a protein responsible for healthy joints and elastic skin throughout the body. When researchers cut through the cell layer (like how if you injure your skin), the fibroblasts moved into the gash quickly to fill it, unlike the older cells.

Though the findings are quite encouraging, were still some ways from seeing this new de-aging technique used in a clinical setting. Experts also have some lingering questions regarding how long exactly this rejuvenation lasts and whether the new technique actually improves a cells lifespan.

The authors only looked for a short period of time after [applying Yamanaka factors] but what happens once the cell has divided a few times? Does the molecular clock catch up? asked Sen. The authors also never tested whether the de-aged fibroblasts behaved as younger fibroblasts in live animal models. This question would need to be addressed before this can be used as therapy.

Whether this is the key to the Fountain of Youth remains to be seen.

Dr. Johann Gudjonsson, University of Michigan

Dr. Johann Gudjonsson, a dermatologist who studies inflammatory skin conditions at The University of Michigan and wasn't involved in the study, is also skeptical of the experiment.

Whether this is the key to the Fountain of Youth remains to be seen, Gudjonsson told The Daily Beast in an email. He explained that telomeres, which are the caps binding the ends of DNA and shorten as we age, didnt appear to improve with the new studys treatment. Therefore while the function and state of the cells are rejuvenated it may not mean that their lifespan has changed, he said.

Even if longevity and immediate clinical applications arent in the cards, this new study does offer an interesting proof of concept for future medical research and potentially combating aging.

If this process can be applied to other cell types, one can imagine rejuvenating that particular cell type and using it to restore an aged/failing organ, said Sen. I believe this line of research has a lot of potential and we are just starting to understand the rules of how to reprogram cells.

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CAR T-cell therapy currently in UC Davis Health clinical trial study as potential cure for HIV – The Aggie – The Aggie

Posted: April 19, 2022 at 1:50 am

CAR T-cell immunotherapy may become the alternative option to current life-long retroviral therapy for HIV patients

By BRANDON NGUYEN science@theaggie.org

According to the Joint United Nations Programme on AIDS/HIV or UNAIDS, around 38 million people worldwide live with HIV, a retrovirus that destroys a hosts own immune cells and can progress into AIDS if left untreated. To put this into perspective, around 150,000 people are living with HIV but 68% of them are virally suppressed due to adherence to life-long retroviral therapy.

In efforts to search for an alternative option to life-long treatment, UC Davis Health has commenced a study testing the efficacy of Chimeric Antigen Receptor T-cell Therapy (CAR T-cell Therapy) and its potential as a cure for HIV. CAR T-cell therapy involves the removal of a patients immune systems T-cells and genetically modifying them to recognize and attack HIV-afflicted cells in the host.

Dr. Mehrdad Abedi, a professor of internal medicine, hematology and oncology at UC Davis Health and the principal investigator of the study, further explained the process in administering CAR T-cell therapy to a patient.

For this study, we will educate the cells by inserting a gene to target cells that have been infected by the HIV virus, Abedi said. The idea is these modified cells will attach to the HIV-infected cells and destroy the cells that are infected while also stopping the infected cells ability to replicate.

Modification of human patient T-cells into CAR T-cells has revolutionized patient care, especially for cancer patients. This technology has become widely used in the field of oncology and blood cancer patients, as training ones T-cells to recognize tumors from normal, healthy cells is a novel method to search and destroy tumor cells throughout the blood. This would be impossible with radiation or surgery.

Dr. Paolo Troia-Cancio, a clinical professor of medicine with the infectious disease division and co-investigator for the HIV study, described how the study came about as a result of success stories of patients with HIV and cancer.

It has been shown to be possible to cure HIV because so far there have been three individuals that have been cured of HIV, but they have required bone marrow transplants, Troia-Cancio said. Two of the three patients were administered more conventional allergenic bone marrow transplants and the third person got a transplant from cord blood stem cells. I hope with this type of research that we take what we have learned from these three individuals and apply them in a way that we could modify a patients immune system in a way to make it resistant to HIV.

However, bone marrow transplants are not the ideal or first option for patients with HIV.

While these stories provide inspiration and hope to finding a cure for HIV, a bone marrow transplant is not a realistic option for most patients, Abedi said. Such transplants are highly invasive and risky, so they are generally offered only to people with cancer who have exhausted all other options.

Nonetheless, these three fortunate cases offer hope for a cure, or at least a functional cure, which Troia-Cancio explained as patients being able to control their HIV without medication. With an optimistic outlook for HIV patients, Troia-Cancio underscored the potential for CAR T-cell therapy to revolutionize the healthcare industry in treating other immunological disorders.

There are other diseases where CAR T-cells are being looked at, Troia-Cancio said. So I think theres a potential for this therapy to become more widely used for other areas where having essentially a modified immune system could potentially lead to either long term control or omission or even a cure for a disease.

Written by: Brandon Nguyen science@theaggie.org

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Aurion $120m to advance cell therapy candidate – BioProcess Insider – BioProcess Insider

Posted: April 19, 2022 at 1:50 am

The funding will be used to develop Aurion Biotechs first candidate, AURN001, a cell therapy aiming to treat corneal edema.

Aurion Biotech is a clinical-stage biotech firm that is aiming to restore vision to millions of patients with its regenerative therapies. According to the firm, the raised funds will be used to file an IND to the US Food and Drug Administration (FDA) in order to begin clinical trials.

Additionally, Aurion wants to submit an NDA to the Japan Pharmaceuticals and Medical Devices Agency (PMDA).

Image: Stock Photo Secrets

Funds will be used to advance the clinical development of our cell therapy for corneal edema [AURN001], secondary to corneal endothelial disease, Judith McGarry, vice president marketing at Aurion told BioProcess Insider.

The endothelium is a single layer of cells in the human cornea; it regulates hydration of the cornea. When those cells degrade or die (due to disease or surgical trauma), they do not regenerate. Once those cells are gone, the cornea become swollen and cloudy, ultimately causing loss of vision.

The cell therapy was developed by Shigeru Kinoshita and his colleagues at Kyoto Prefecture University of Medicine (KPUM) in Japan. Aurion acquired this technology in 2020 and is preparing to submit a Japanese new drug application (J-NDA).

First, our inventor was able to figure out how to get human corneal endothelial cells (HCECs) to replicate in the lab (keep in mind, they do not replicate in the body). With this patented process, the cells from a single donor can be manufactured to treat up to 100 eyes, said McGarry.

She continued: This alone is a significant benefit since there is a global shortage of donor corneas available for transplant. Second, the cell therapy procedure itself is relatively straightforward, and can be performed in an outpatient setting, in approximately 15 minutes. The ophthalmologist makes an incision into the anterior chamber of the patients eye, and polishes off the diseased endothelial cells. Then, via another incision, the ophthalmologist injects HCECs in solution into the anterior chamber. The cells quickly settle into place, along the stroma of the cornea [and] the patient lies face down for a couple of hours, to facilitate adhesion.

The $120 million financing was led by Deerfield Management, and included current investors Flying L Partners, Falcon Vision, KKR, Visionary Ventures, and Petrichor Healthcare Capital Management. Furthermore, funds will be paid out to Aurion based on specific achievements of clinical and operational milestones.

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ExCellThera announces new publication showing its ECT-001 cell therapy improves transplant access for all patients – BioSpace

Posted: April 19, 2022 at 1:50 am

MONTREAL, April 13, 2022 (GLOBE NEWSWIRE) -- ExCellThera Inc. (ExCellThera), an advanced clinical-stage biotechnology company delivering molecules and bioengineering solutions to expand and engineer various cell lines for use in next generation cell and gene therapies, announced today the publication of a scientific article entitled UM171 expansion of cord blood improves donor availability and HLA matching for all patients, including minorities. The study by Dumont-Lagac et al., was recently published in the peer-reviewed medical journal Transplantation and Cellular Therapy.

Using data from the Be The Match donor and cord blood registry, the retrospective study concluded that expansion with UM171:

UM171 is the proprietary molecule used in ExCellTheras lead technology, ECT-001, a cell therapy under development being evaluated in several clinical trials in the United States and Canada.

A persistent problem under the current standard of care for allogeneic stem cell transplantation is finding a suitable donor for all patients. While cord blood units cryopreserved in public banks offer a readily available source of stem cells for transplantation, the low number of cells they contain have hampered their use. This new study demonstrates how expanding small cord blood units results in a greater access to transplantation.

The results of this study are supported by what we have seen in our clinical trials, where weve been able to identify a cord suitable for expansion for all patients enrolled, no matter their ethnic origin, said Dr. Pierre Caudrelier, Chief Medical Officer of ExCellThera. Furthermore, thanks to the low starting cell dose requirement for UM171 expanded grafts, about half of the patients in our first Phase I/II trial benefited from better HLA matching than would have been possible without expansion.

About ExCellThera Inc.

ExCellThera is a clinical-stage cell expansion and engineering company delivering molecules and bioengineering solutions to expand and engineer various cell lines for use in novel one-time curative therapies for patients with hematologic malignancies and other diseases. ExCellTheras most advanced technology, ECT-001, a cell therapy, combines a proprietary molecule, UM171, and an optimized culture system. In pursuit of better treatments for patients, the company is building out its cell expansion and engineering platform, as well as supporting best-in-class clinical trials. excellthera.com

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New CAR T-Cell Therapy for Solid Tumors Was Safe and Showed Early Efficacy – The ASCO Post

Posted: April 19, 2022 at 1:50 am

By The ASCO Post StaffPosted: 4/13/2022 12:05:00 PM Last Updated: 4/13/2022 1:12:21 PM

A new chimeric antigen receptor (CAR) T-cell product had an acceptable safety profile and showed early signs of efficacy as a monotherapy and in combination with an mRNA vaccine in patients with solid tumors, according to preliminary data from a phase I/II clinical trial presented by Haanen et al during the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract CT002).

CAR T-cell therapy has revolutionized the treatment options for hematologic malignancies, but its application in solid tumors has been challenging. One of the main limitations is that most of the proteins present on solid tumors that could be used as targets are also found at low levels on normal cells, making it difficult to specifically direct the CAR T cells against tumor cells and spare healthy ones, said lead author John Haanen, MD, PhD, a medical oncologist at the Netherlands Cancer Institute (NKI), Amsterdam. Other challenges include the limited persistence of CAR T cells observed in solid tumors and their difficulty reaching the tumors and penetrating the center of the mass.

Dr. Haanen and colleagues are conducting a first-in-human open label, multicenter clinical trial to evaluate the safety and preliminary efficacy of a previously developed CAR T-cell product that targets CLDN6, a tumor-specific antigen widely expressed in various solid tumors but silenced in healthy adult tissues. This therapy was tested in preclinical models in combination with a CLDN6-encoding mRNA vaccine (CARVac) that favors the expansion of the CAR T cells. As Dr. Haanen explained, this combined treatment, called BNT211, resulted in expansion of the transferred CAR T cells and higher persistence in the blood, which in turn improved tumor cell killing.

Methodology and Findings

The investigators recruited patients with relapsed or refractory advanced, CLDN6-positive solid tumors to test the CLDN6 CAR T-cell therapy alone and in combination with CARVac.

The trial included two parts in which increasing doses of CLDN6 CAR T cells were given as monotherapy (part 1) and in combination with CARVac (part 2), following lymphodepletion to reduce the number of T cells present in the body and make room for the transferred CAR T cells. In part 2, CARVac was administered every 2 or 3 weeks up to 100 days after the CAR T-cell transfer, and one patient received maintenance vaccinations every 6 weeks. Overall, 16 patients had been treated at the time of this reporting.

Approximately 40% of patients developed manageable cytokine-release syndrome without any signs of neurotoxicity. Other adverse events included cytopenia and abnormal immune responses, all of which were resolved. Administration of CARVac resulted in transient flu-like symptoms that lasted up to 24 hours. CLDN6 CAR T treatment and CARVac appeared to be safe, with only limited and manageable adverse events, said Dr. Haanen.

Among the 14 patients who were evaluable for efficacy, at 6 weeks after infusion, four patients with testicular cancer and two with ovarian cancer experienced a partial response, with an overall response rate of nearly 43%. Among the study participants who had a partial response, four patients received CAR T cells as a monotherapy and two patients were treated with the CAR TCARVac combination. The disease control rate was 86%. In all evaluable patients, deepening of initial partial responses was observed at 12 weeks after infusion. This resulted in one complete response that has continued 6 months after infusion.

It is remarkable that most of the patients with testicular cancer showed clinical benefit at dose level 2, and the responses we have observed can be deep, including one ongoing complete remission, said Dr. Haanen.

Study Implications

The infusion of CLDN6 CAR T, alone or in combination with CARVac, is safe and holds promise for patients with CLDN6-positive cancers, Dr. Haanen added. CLDN6 was never targeted before with cellular therapy, but in our study, this approach is already showing efficacy that may be better than the data from other CAR T trials in solid tumors.

However, Dr. Haanen cautioned that these data are very early, with few patients having been treated, so no major conclusions can be drawn at this time.

Disclosure: The study was sponsored by BioNTech SEs subsidiary BioNTech Cell & Gene Therapies GmbH. NKI received research grants from BioNTech. Dr. Haanen is on the scientific advisory board of BioNTech. Financial compensation goes to NKI. For full disclosures of all study authors, visit abstractsonline.com.

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Paul Laikind, PhD, Joins Stemson Therapeutics Board of Directors – Business Wire

Posted: April 19, 2022 at 1:50 am

SAN DIEGO--(BUSINESS WIRE)--Stemson Therapeutics Corp., a private biotechnology company developing an iPSC-derived autologous cell therapy to regenerate healthy hair follicles, announced today that Paul Laikind, serial entrepreneur and former CEO of cell therapy company ViaCyte, has joined the Stemson Board of Directors. Paul brings significant company building and therapeutics development experience to the Stemson Board.

We welcome Paul as an important addition to our board of directors, said Matt Posard, Stemsons executive chairman of the board. With more than 35 years of experience founding and leading therapeutics development companies from preclinical to clinical stage development and from start-up through IPO, Paul will provide valuable guidance to accelerate Stemsons progress.

I am delighted and honored to join Stemsons Board of Directors, said Paul. Stemsons unique combination of novel technologies to bioengineer hair follicles not only has the potential to help millions of people suffering from hair loss, but can more broadly advance the capabilities for cell therapy development across the industry. I look forward to working with the team and supporting their journey.

Paul Laikind, PhD, was CEO of ViaCyte from 2012 until 2020, where he lead the development of the first stem cell-derived cell therapies designed to replace pancreatic beta cells for the treatment of Type 1 Diabetes. Paul led the company from the preclinical stage through the introduction of two product candidates into clinical trials before retiring at the end of 2020. A third product that Viacyte developed in collaboration with CRISPR Tx recently also entered clinical development.

Dr. Laikind served as Chief Business Officer and Senior Vice President of the Sanford Burnham Medical Research Institute from 2009 2011, focusing on enhancing the translational capabilities of the institute. From 1999 - 2009, Paul was cofounder and CEO of Metabasis Therapeutics, which concentrated on therapeutics development for metabolic and liver diseases. He took Metabasis from founding through IPO, and from preclinical to clinical stage development, with five products in the clinic. From 1986 1999, Paul cofounded and served as Vice President of Corporate Development at Gensia Pharmaceuticals where they developed small molecule therapies for the treatment of cardiovascular, neurological and inflammatory diseases. During that time, he cofounded and served as an advisor to Viagene from 1988 1994, the first commercially focused gene therapy company developing proprietary gene delivery technology to treat HIV, cancer and inherited disorders. Gensia, Viagene and Metabasis each completed successful initial public offerings and were eventually acquired for combined proceeds of over $3.5 billion.

Throughout his career, Dr. Laikind has played a leadership role in the evolving biotechnology industry. He serves or has served on the board of industry organizations including BIO, BIOCOM, CONNECT, and Alliance for Regenerative Medicine.

Paul earned his PhD in Biochemistry from the University of California, San Diego, and is a veteran of the US Navy.

We are very lucky to have Paul join us. The next stage of Stemsons development is to advance our first product toward human clinical trials, stated Geoff Hamilton, cofounder and CEO of Stemson Therapeutics. Pauls tremendous business leadership experience and industry relationships, as well as his involvement developing similar technologies to Stemsons while at ViaCyte, will help us guide the company toward that goal.

About Stemson Therapeutics

Stemson Therapeutics is a pre-clinical stage cell therapy company founded in 2018 with a mission to cure hair loss by leveraging the regenerative power of Induced Pluripotent Stem Cells. Based on the breakthrough innovation by Stemson Therapeutics co-founder, Dr. Alexey Terskikh, Stemson uses iPSC to regenerate the critical cells required to grow hair and which are damaged or depleted in patients suffering from hair loss. The iPSC-derived cells are used to grow de novo hair follicles, offering a new supply of hair to treat people suffering from various forms of Alopecia. Today, there are no available treatments capable of growing new hair follicles. Stemsons world class team of scientists, advisors and collaborators are passionate about delivering a scientifically based, clinically tested cure for hair loss to the millions of hair loss sufferers who seek help for their hair loss condition. Stemson Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.stemson.com.

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Paul Laikind, PhD, Joins Stemson Therapeutics Board of Directors - Business Wire

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Designing effective contamination prevention strategy: Crucial factors to consider for cell therapy production on SelectScience – SelectScience

Posted: April 19, 2022 at 1:50 am

In advanced therapy medicinal products (ATMP) manufacturing, the quality and safety of the product needs to be ensured from the first stages of development. Discover how to design an effective contamination prevention strategy that will minimize risks to cell therapy products and allow you to implement appropriate control measures.

The webinar will outline the types and sources of particulates in a cell therapy production environment and their impact on product quality and safety. It will also explore the role of laboratory equipment in contamination prevention, and provide clarity around regulatory requirements, validation methodology, and the validation process for laboratory equipment.

Key learning objectives

Who should attend?

Lab scientists, lead scientists, R&D scientists, principal investigators, engineers and lab or facility managers involved in the cell therapy development journey starting from R&D and pre-clinical / clinical testing (translational institutes, medical institutes, academic incubators, GMP production facilities) through to the later stages of cell therapy development, such as commercialisation / scale up and QC testing, usually taking place in Biotech, Biopharma, Contract Research Organisations (CRO), Contract Manufacturing Organisations (CMO) & Contract Development and Manufacturing Organizations (CDMO).

This webinar will be of interest to principal investigators, lead scientists, research scientists, lab managers, facility managers, process engineers, and others working in this field.

Certificate of attendance

All webinar participants can request a certificate of attendance, including a learning outcomes summary, for continuing education purposes.

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Designing effective contamination prevention strategy: Crucial factors to consider for cell therapy production on SelectScience - SelectScience

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Gene found to block small-cell lung cancer proliferation in mice – Medical News Today

Posted: April 19, 2022 at 1:50 am

The research, which appears in the journal Science Advances, lays the groundwork for developing future cancer treatments for humans.

An estimated 13% of diagnosed lung cancer is SCLC. According to the National Organization for Rare Diseases, SCLC is an aggressive type of cancer characterized by rapid, uncontrolled growth of certain cells in the lungs.

If SCLC is caught early and before it has spread, treatments can control the disease in up to 25% of cases.

The authors of the recent study wanted to understand the role of EP300 gene mutations in SCLC.

Medical News Today spoke with the corresponding authors of the study:

The current prognosis for SCLC patients is particularly poor with only 7% of patients surviving beyond 5 years. This reflects a lack of well-validated targets for therapy and a concomitant lack of targeted agents to treat the disease, they explained.

It is critical to garner further insights as to the drivers of the disease as well as develop drugs targeting those drivers. However, relevant pre-clinical models of SCLC carrying recurrent driver mutations were scarce, precluding the study to assess the physiological role of the mutations and the therapeutic impact of restoring their normal functions. So we built pre-clinical models using genetically engineered mice and cells.

By studying genetically engineered mouse models, the researchers found that EP300 the protein that the EP300 gene codes for can either promote or inhibit SCLC.

Specifically, they found that part of the EP300 protein known as the KIX domain was essential for the development of SCLC.

EP300 is a multi-functional protein and loss of its histone acetyltransferase domain function as predicted based on the mutations observed in SCLC patient tumors drives the cancer. This idea was validated by the findings from the pre-clinical models, they explained.

Unexpectedly, however, the models also showed that the KIX domain of the mutant EP300, which remains intact, drives the disease. Specifically, the protein-protein interactions mediated by the KIX domain of EP300 are critical for the survival of SCLC cells and vulnerable to inhibition. This was shown both in a mouse model as well as using human SCLC cell lines.

This validates the KIX domain of EP300 as a target for drug development for the treatment of SCLC, specifically a protein-protein interaction inhibitor of the KIX domain, said Drs. Park and Bushweller.

The finding may also have relevance for other types of cancer. According to the corresponding authors, EP300 mutations are widespread and have been implicated as having a critical role in other cancers including leukemia and triple-negative breast cancer.

MNT spoke with Dr. Charles Evans, research information manager at Cancer Research UK, who was not involved in the study.

This work highlights a key vulnerability that could be a target for potential new treatments, not only for small-cell lung cancer but also for other cancer types.

Dr. Evans

Right now, we only have a limited range of chemotherapy treatments available for people with small-cell lung cancer many of which can have harsh side effects, said Dr. Evans.

This study highlights a potential vulnerability for small-cell lung cancers, which could be exploited with new, targeted drugs in the future. However, more studies will be needed to confirm these results and develop a new treatment approach.

Dr. Evans said that the findings were one of a number of potential new treatment options for cancer.

There are other promising areas of research that are happening right now, such as the development of immunotherapies that can harness the power and precision of our immune systems to tackle cancer.

And innovations in radiotherapy, including new techniques such as proton beam therapy, have the potential to target tumors with a stronger dose far more precisely, limiting damage to surrounding tissue and reducing the burden of long-term side effects from treatment.

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Gene found to block small-cell lung cancer proliferation in mice - Medical News Today

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