Category Archives: Cell Biology

Cell Biology

City of Hope Enters Licensing Agreement With Chimeric to Develop Its Pioneering Chlorotoxin CAR T Cell Therapy – Business Wire

DUARTE, Calif.--(BUSINESS WIRE)--City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases, today announced that it has licensed intellectual property relating to its pioneering chlorotoxin chimeric antigen receptor (CLTX-CAR) T cell therapy to Chimeric Therapeutics Limited, an Australian biotechnology company.

The therapy is currently being used in a phase 1 clinical trial at City of Hope to treat glioblastoma (GBM), a type of brain tumor. The first patient in the trial was recently dosed; Behnam Badie, M.D., chief of City of Hopes Division of Neurosurgery and The Heritage Provider Network Professor in Gene Therapy, is leading this innovative, first-of-its-kind trial.

Chimeric has acquired the exclusive worldwide rights to develop and commercialize certain patents relating to City of Hopes CLTX-CAR T cells, as well as to further develop the therapy for other cancers.

City of Hope is excited to enter into this agreement with Chimeric as it supports our innovative research in CAR T cell therapy and our commitment to extend these therapies to more patients, particularly those with GBM and other solid tumors that are difficult to treat, said Christine Brown, Ph.D., The Heritage Provider Network Professor in Immunotherapy and deputy director of City of Hopes T Cell Therapeutics Research Laboratory. Chimeric shares our goal of providing effective CAR T cell therapies to more patients with current unmet medical needs.

Led by Brown and Michael Barish, Ph.D., chair of City of Hopes Department of Developmental and Stem Cell Biology, and Dongrui Wang, Ph.D., a recent graduate of City of Hopes Irell & Manella Graduate School of Biological Sciences, the team developed and tested the first CAR T cell therapy using CLTX, a component of scorpion venom, to direct T cells to target brain tumor cells. The research was published this past March in Science Translational Medicine.

Chimeric is excited to join City of Hope in its quest to find more effective cancer therapies. This is an exceedingly rare opportunity to acquire a promising technology in one of the most exciting areas of immuno-oncology today, said Paul Hopper, executive chairman of Chimeric. Furthermore, the CLTX-CAR T cell therapy has completed years of preclinical research and development, and recently enrolled its first patient in a phase 1 clinical trial for brain cancer.

CARs commonly incorporate a monoclonal antibody sequence in their targeting domain, enabling CAR T cells to recognize antigens and kill tumor cells. In contrast, the CLTX-CAR uses a synthetic 36-amino acid peptide sequence first isolated from death stalker scorpion venom and now engineered to serve as the CAR recognition domain.

In this recent study, City of Hope researchers used tumor cells in resection samples from a cohort of patients with GBM to compare CLTX binding with expression of antigens currently under investigation as CAR T cell targets. They found that CLTX bound to a greater proportion of patient tumors, and cells within these tumors.

CLTX binding included the GBM stem-like cells thought to seed tumor recurrence. Consistent with these observations, CLTX-CAR T cells recognized and killed broad populations of GBM cells while ignoring nontumor cells in the brain and other organs. The study team demonstrated that CLTX-directed CAR T cells are highly effective at selectively killing human GBM cells without off-tumor targeting and toxicity in cell-based assays and in animal models.

City of Hope, a recognized leader in CAR T cell therapies for GBM and other cancers, has treated more than 500 patients since its CAR T program started in the late 1990s. The institution continues to have one of the most comprehensive CAR T cell clinical research programs in the world it currently has 30 ongoing CAR T cell clinical trials, including CAR T cell trials for HER-2 positive breast cancer that has spread to the brain, and PSCA-positive bone metastatic prostate cancer. It was the first and only cancer center to treat GBM patients with CAR T cells targeting IL13R2, and the first to administer CAR T cell therapy locally in the brain, either by direct injection at the tumor site, through intraventricular infusion into the cerebrospinal fluid, or both. In late 2019, City of Hope opened a first-in-human clinical trial for patients with recurrent GBM, combining IL13R2-CAR T cells with checkpoint inhibitors nivolumab, an anti-PD1 antibody, and ipilimumab, blocking the CTLA-4 protein.

Both an academic medical center and a drug development powerhouse, City of Hope is known for creating the technology used in the development of human synthetic insulin and numerous breakthrough cancer drugs. Its unique research and development hybrid of the academic and commercial creates an infrastructure that enables City of Hope researchers to submit an average of 50 investigational new drug applications to the U.S. Food and Drug Administration each year. The institution currently holds more than 450 patent families.

"City of Hope is delighted to license this technology to Chimeric, said Sangeeta Bardhan Cook, Ph.D., City of Hope director of the Office of Technology Licensing. We are impressed with the ability of their executive team to push and bring therapies to market expeditiously. At City of Hope, our mission is to transform the future of health care. We believe Chimeric has the vision to offer innovative therapies to cancer patients.

About City of Hope

City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hopes translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope has been ranked among the nations Best Hospitals in cancer by U.S. News & World Report for 14 consecutive years. Its main campus is located near Los Angeles, with additional locations throughout Southern California. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.

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City of Hope Enters Licensing Agreement With Chimeric to Develop Its Pioneering Chlorotoxin CAR T Cell Therapy - Business Wire

Cell Biology

Shared protein fingerprint could simplify treatment of common inherited heart disease – Newswise

Newswise MADISON, Wis. Hypertrophic cardiomyopathy is the most common inherited heart disease, marked by an abnormally thickened heart muscle that can obstruct blood flow and lead to sudden death in young adults.

A dizzying array of over 1,400 genetic mutations can lead to the disease, puzzling doctors on how to treat so many unique varieties. But in new research, University of WisconsinMadison scientists discovered that many different genetic mutations result in surprisingly similar changes to heart muscle proteins in patients with the most severe manifestations of hypertrophic cardiomyopathy. This shared protein fingerprint suggests that shared treatments could treat the disease.

This could be good news for doctors treating obstructive hypertrophic cardiomyopathy patients, because our data suggest theres a convergent pathway in these patients, allowing development of treatments that generally target patients with severe obstruction from their cardiomyopathy instead of targeting a patient's individual genetic mutations, says Ying Ge, a professor of cell and regenerative biology and chemistry at UWMadison who headed the new study.

Ge and an international collaboration of researchers published their findings the week of Sept. 21 in the Proceedings of the National Academy of Sciences. UWMadison graduate students Trisha Tucholski and Wenxuan Cai led the work, which analyzed in detail the protein signatures of diseased and normal hearts using advanced protein-measurement technology.

The team collected samples of diseased heart tissue from 16 patients who underwent corrective surgery to fix impaired blood flow in their hearts. Hypertrophic cardiomyopathy in eight of these patients was due to eight distinct mutations across two genes; for the other eight patients, the disease-causing mutations were unknown. Proteins from the diseased heart samples were compared to those from healthy donor hearts.

Despite the variation in underlying genetic mutations, Ges team discovered a general pattern in hearts from patients with the disease. For example, many key muscle proteins from diseased hearts had fewer molecular tags known as phosphates. While the exact consequence of having fewer phosphates is unknown, its likely that these altered proteins contribute to a general state of dysregulation in the heart, leading to the thickened muscle characteristic of the disease.

The findings reinforce that genetic mutations arent always enough to explain diseases, says Ge. The proteins those genes encode have the ultimate impact on health, and the bodys proteins can be altered in subtle but consequential ways during disease.

When we first performed these experiments, this similarity at the protein level was quite surprising to us because it is generally expected that different mutations could lead to different changes in the proteins, says Ge. But in reality, these results make sense, because when the patients with this disease present to the hospital for surgery, their hearts exhibit similar dysfunction.

The results are still preliminary. Ges group wants to expand to study hundreds of additional patients with a wide array of underlying hypertrophic cardiomyopathy mutations to see if the similar protein fingerprint trend holds. They also plan to study heart stem cells with disease-causing mutations in an effort to study early stages of the disease, which isnt possible with human patients.

But with additional research, this kind of in-depth analysis of protein fingerprints could guide future treatments.

This data opens the door with evidence showing that protein-level changes might be a better reflection of the patients disease than their genes, and if we can examine patients' samples at the protein level, that could help us provide precision-medicine treatments, says Ge.

This work was supported in part by the National Institutes of Health (grants R01 HL096971, R01 GM117058, GM125085, HL109810, S10 OD018475, T32 GM008505, T32 GM008688, R01 HL129798, U01 HL134764, and R01 HL139883) and the National Science Foundation (grant EEC-1648035).

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Shared protein fingerprint could simplify treatment of common inherited heart disease - Newswise

Cell Biology

Researchers identify a compound that inhibits growth of schwannomas – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Sep 21 2020

Schwannomas are tumors of the peripheral nervous system, which often occur in the genetic disease neurofibromatosis type 2.

The research group of Prof. Dr. Helen Morrison at the Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) in Jena, Germany, identified a compound that inhibits the growth of such tumors and improves nerve function.

In a new project, the group will now conduct a multi-center preclinical study together with three German partners. The BMBF is funding this step towards a therapeutic application with a grant of 1.45 million euro over 3 years.

Jena. A schwannoma is a benign tumor of the peripheral nervous system. It usually results from an abnormal overgrowth of Schwann cells, a cell type covering nerve fibers and supporting them in their function.

Following nerve damage, Schwann cells divide to support regeneration in sufficient numbers. However, if cell division is not limited in time, over-proliferation of Schwann cells occurs and causes schwannoma formation.

These progressively growing tumors compress nerve cells, impairing nerve function and causing symptoms such as paralysis or pain.

Schwannomas often appear in the context of the hereditary disease neurofibromatosis type 2 (NF2), which causes uncontrolled growth of nervous and connective tissues, particularly surrounding the 8th cranial nerve. Consequently, loss of hearing and balance are frequent symptoms of NF2.

Prof. Dr. Helen Morrison and her research group "Nerve Regeneration" at the Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) in Jena, Germany, is studying the role of Schwann cells in the peripheral nervous system.

The team was able to identify a molecule that inhibits schwannoma growth. The protein Neuregulin 1 (Nrg1) occurs naturally in the body and induces differentiation of Schwann cells, including termination of cell division following nerve regeneration.

However, in the case of the hereditary disease NF2 and likely other schwannomas, Nrg1 is strongly downregulated. Without this stop signal, Schwann cells fail to differentiate, continue to divide and form schwannomas.

Therapy options are very limited and focus on surgical removal, often causing additional nerve damage and entailing a high recurrence rate. Novel approaches are urgently needed to improve tumor therapy and patient's quality of life.

Prof. Dr. Morrison's group has already shown that Nrg1 inhibits schwannoma growth and improves nerve function in a mouse model.

Her current project aims to develop this approach further towards clinical application. Previous studies on heart diseases have classified Nrg1 as safe for use in humans.

Now, the research group has successfully obtained funding to conduct a multi-centric, preclinical study. Starting from August 2020, the German Federal Ministry of Education and Research (BMBF) will fund this study for 3 years with a total sum of 1.45 million euro, of which approximately 732,000 euro will go to FLI.

We are very pleased about this support and see this as encouragement of our research," says Prof. Morrison, who has many years of experience in research on the hereditary disease NF2. "Together with our partners we hope to contribute to the development of a drug to help people affected by this disease."

Headed by Prof. Dr. Morrison of the FLI, the research team also includes the partner laboratories of Dr. Robert Fledrich and Dr. Ruth Stassart of the University Hospital Leipzig and Prof. Dr. Reinhard Bauer at the Institute of Molecular Cell Biology of Jena University Hospital.

The teams' research approach is unprecedented: Following standards of clinical patient trials, three centers will conduct parallel, randomized and blinded experiments following a preregistered study protocol.

Study design as well as statistical data analysis is conducted independently by the team of Prof. Dr. Andr Scherag of the Institute for Medical Statistics, Computer and Data Sciences of Jena University Hospital. Collectively, these measures strongly increase the studies' validity and significance.

The research network will be further supported by a funded membership of the TMF (Technologie- und Methodenplattform fr die vernetzte medizinische Forschung e.V.), that will enable a broad exchange with experts on diverse methods crucial to networked medical research (e.g. research data management).

Additionally, all projects of the current BMBF funding line will be counseled by the partner project "DECIDE" located at the Charit in Berlin.

We are looking forward to the interaction with all these different experts to apply highest standards to our preclinical study."

Dr. Helen Morrison, Professor, Leibniz Institute on Aging - Fritz Lipmann Institute

The new BMBF funding line for preclinical studies supports innovative research projects aiming to expedite translation of important research findings from basic research to clinical application. This aim is shared by the [emailprotected] program, which supported the preceding work leading up to the current preclinical study.

Dr. Sonja Schtzlein, head of [emailprotected], sees the current funding as a success: "I am pleased to see that SPARK has contributed to advancing the project to this important step towards an application-oriented therapy by providing financial support, advice and arranging mentoring partners from industry."

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Researchers identify a compound that inhibits growth of schwannomas - News-Medical.Net

Cell Biology

Enhancing overall facial skin wellness: Augustinus Bader reveals The Face Oil – The Moodie Davitt Report – The Moodie Davitt Report

Augustinus Bader is a Silver Partner of The Moodie Davitt Virtual Travel Retail Expo where it is exhibiting in #Virtual Stand BT-S9

Augustinus Bader a Silver Partner at the upcoming Moodie Davitt Virtual Travel Retail Expo has extended its luxury skincare range with The Face Oil.

The new Face Oil offers an ultra-lightweight, fast-absorbing and nourishing formula made with an exact calibration of cold-pressed oils and the brands patented TFC8 technology.

Augustinus Bader is a London-based science-driven premium skincare brand. It was launched in 2018 to help fund research into burn repair, skin graft prevention and scar minimisation.

The brand was founded by Professor Augustinus Bader who is a pioneer in the field of stem cell biology. Backed by more than 30-years of research and innovation, Bader developed a ground-breaking wound-gel in 2008 that helped regenerate skin affected by third-degree burns without surgery.

The Face Oil leverages Professor Augustinus Baders extensive stem cell biology expertise. It instantly hydrates the skin and retains moisture without leaving any greasy residue. It also minimises fine lines and wrinkles, reduces hyper-pigmentation and boosts cellular renewal.

The Face Oil offers a powerful blend of Babassu Oil, Argan Oil, Hazelnut Oil, Karanja Oil and TFC8

The Face Oil is made with a potent blend of Babassu Oil, Argan Oil, Hazelnut Oil, Karanja Oil and TFC8. Babassu Oil is a vitamin-rich seed oil which protects the skin against environmental aggressors, while Argan oil helps restore the skins hydrolipidic film and prevents trans-epidermal water loss.

Hazelnut Oil supports the skins moisture retention, while Karanja Oil delivers soothing antimicrobial properties and prevents premature ageing. Finally, TFC8 an exclusive patented complex of amino acids and vitamins boots internal skin repair and renewal.

We wanted to offer our customers the option between a rich cream, a light cream, and now, an oil, so they can select the texture that works best for their facial skincare routine, commented Professor Bader. Each of these offerings contains our specialised compound TFC8, which transport natural mechanisms for skin repair. As long as you have one product with TFC8, you will see results.

Augustinus Bader officially launched The Cream and The Rich Cream in 2018. The brand made its travel retail debut at TFWA World Exhibition in Cannes in 2019 and plans to further extend its footprint in the channel at the upcoming Moodie Davitt Virtual Travel Retail Expo this October, where it is exhibiting at #Virtual Stand BT-S9.

Professor Augustinus Bader leverages more than 30 years of stem cell biology expertise to formulate his luxury skincare range

Augustinus Bader is a Silver Partner at the inaugural Moodie Davitt Virtual Travel Retail Expo.

The unique 5-day live event, followed by a 30-day showcase, begins on 12 October, just after the conclusion of the Chinese Golden Week holidays. It features a star-studded series of events across the five days, including a Symposium, category workshops and a new consumer research initiative.

Registration is free for buyers, exhibitors and preferred media partners. (Clickhereto register)

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Enhancing overall facial skin wellness: Augustinus Bader reveals The Face Oil - The Moodie Davitt Report - The Moodie Davitt Report

Cell Biology

University of Edinburgh spinout Cellinta will develop gene therapies for cancer – PharmaTimes

A biotech company spun out of the University of Edinburgh will utilise research to develop new gene therapies to target different types of cancer.

The company, Cellinta Limited, was born out of research from scientists at the University of Edinburgh, and received funding through investments from SV Health Investors and Cancer Research UK.

The funding will be used to develop a pipeline of highly selective gene therapies targeting cancer stem cells in a variety of solid tumour types.

It will draw on research led by Professor Steven Pollard at the University of Edinburgh, which delved into stem cell biology, synthetic biology and cancer genomics.

Cellinta has entered into a collaborative research agreement with the University, and retains the option to license intellectual property developed from research conducted there.

Professor Pollard will join the Cellinta team as scientific founder and a senior adviser, while Dr Soraya Bekkali will take the helm as chief executive officer of the new company.

I am delighted to be leading such an exciting company, said Dr Bekkali.

Cellintas approach offers the opportunity to deliver combinations of therapies selectively to cancer stem cells, bypassing the limitations of traditional treatments which often target single genes or redundant signalling pathways, she added.

Meanwhile, Mike Ross managing partner at London-based SV Health Investors has been appointed chairman of Cellinta.

Cellinta represents a unique opportunity to build a leading company based on exciting and innovative science, with the potential to develop first-in-class therapies, said Ross.

We are delighted with the progress the company has made and extremely pleased to appoint Soraya, who has deep experience in gene therapy across various therapeutic areas, as CEO. We look forward supporting Cellinta in its progress as a pioneer in the field, he added.

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University of Edinburgh spinout Cellinta will develop gene therapies for cancer - PharmaTimes

Cell Biology

A Drug Used to Treat Deadly Coronavirus Infections in Cats May Be an Effective Treatment Against COVID-19 – SciTechDaily

In a search for COVID-19 treatments, researchers pursue a drug used on cats.

University of Alberta researchers worked with SLAC X-ray scientists to explore the potential of a feline coronavirus drug that may be effective against SARS-CoV-2.

Researchers at the University of Alberta have shown that a drug used to treat deadly coronavirus infections in cats could potentially be an effective treatment against SARS-CoV-2, the virus behind the global coronavirus pandemic. Theresults were published in the journal Nature Communications.

The study, which was aided by scientists at the U.S. Department of Energys SLAC National Accelerator Laboratory, paves the way for human clinical trials, which should begin soon, said Joanne Lemieux, a professor of biochemistry at the University of Alberta and the studys senior author.

Joanne Lemieux and a team at the University of Alberta found that a drug used in cats may help treat SARS-CoV-2 infections. Credit: Image courtesy Joanne Lemieux

This drug is very likely to work in humans, so were encouraged that it will be an effective treatment for COVID-19 patients, Lemieux said, although the clinical trials will need to run their course before anyone can be sure that the drug, a protease inhibitor called GC376, is both safe and effective for treating COVID-19 in humans.

In cats at least, GC376 works by interfering with a virus ability to replicate, thus ending an infection. Derivatives of this drug were first studied following the 2003 outbreak of severe acute respiratory syndrome (SARS), and it was further developed by veterinary researchers who showed it cures fatal feline affliction.

Lemieux and colleagues at the University of Alberta first tested two variants of the feline drug against SARS-CoV-2 protein in test tubes and with the live virus in human cell lines, then crystallized the drug variants in conjunction with virus proteins. Working with Silvia Russi, a crystallographer and beamline scientist for the Structural Molecular Biology program at SLACs Stanford Synchrotron Radiation Lightsource (SSRL), the researchers determined the orientation of the cat drug as it bound to an active site on a SARS-CoV-2 protein, revealing how it inhibits viral replication.

This will allow us to develop even more effective drugs, Lemieux said, and the team will continue to test modifications of the inhibitor to make it an even better fit inside the virus.

Aina Cohen, a SLAC senior scientist and co-division head of Structural Molecular Biology at SSRL, said she was excited by the drugs effectiveness and by SSRLs ability to help out. Until an effective vaccine can be developed and deployed, drugs like these add to our arsenal of COVID-19 treatments, she said. We are thrilled to learn of these important results and look forward to learning the outcome of clinical trials.

Reference: Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication by Wayne Vuong, Muhammad Bashir Khan, Conrad Fischer, Elena Arutyunova, Tess Lamer, Justin Shields, Holly A. Saffran, Ryan T. McKay, Marco J. van Belkum, Michael A. Joyce, Howard S. Young, D. Lorne Tyrrell, John C. Vederas and M. Joanne Lemieux, 27 August 2020,Nature Communications.DOI: 10.1038/s41467-020-18096-2

The research was funded by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada. Extraordinary SSRL operations were supported in part by the DOE Office of Science through the National Virtual Biotechnology Laboratory, a consortium of DOE national laboratories focused on response to COVID-19, with funding provided by the Coronavirus CARES Act. SSRL is a DOE Office of Science user facility. The Structural Molecular Biology Program at SSRL is supported by the DOE Office of Science and by the National Institutes of Health, National Institute of General Medical Sciences.

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A Drug Used to Treat Deadly Coronavirus Infections in Cats May Be an Effective Treatment Against COVID-19 - SciTechDaily

Cell Biology

Innovent and Lilly Release Biomarker Results of TYVYT (Sintilimab Injection) in Combination with ALIMTA (Pemetrexed) and Platinum Chemotherapy as…

SAN FRANCISCO and SUZHOU, China, Sept. 20, 2020 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, jointly announce with Eli Lilly and Company ("Lilly", NYSE: LLY) that biomarker results from the ORIENT-11 study were released in a mini oral presentation at the European Society for Medical Oncology (ESMO) Virtual Congress 2020. The ORIENT-11 primary clinical results were released during the IASLC World Conference on Lung Cancer (WCLC) 2020 Virtual Presidential Symposium as an oral presentation and simultaneously published by the Journal of Thoracic Oncology.

ORIENT-11 is a randomized, double-blind, Phase 3 clinical trial evaluating TYVYT (sintilimab injection) or placebo in combination with ALIMTA (pemetrexed) and platinum chemotherapy as a first-line treatment for advanced or recurrent nonsquamous non-small cell lung cancer (nsqNSCLC) without sensitizing EGFR mutations or ALK rearrangements. The National Medical Products Administration (NMPA) of China has accepted the supplemental New Drug Application (sNDA) for this indication. Biomarker data analysis revealed that the MHC-II antigen presentation pathway played a key role in immunotherapy-chemotherapy combination. Higher gene expression of this pathway was significantly associated with longer progression-free survival (HR, 0.41; 95% CI, 0.23-0.76; P=0.0041) and could potentially serve as a predictive biomarker to select patients who can benefit from this regimen.

Professor Li ZHANG, Head of Department of Internal Medicine, Sun Yat-sen University Cancer Center, the primary investigator of the ORIENT-11 trial, stated: "Sintilimab in combination with pemetrexed and platinum chemotherapy showed improved efficacy and no new safety signals in locally advanced or metastatic nonsquamous NSCLC. These results will further our understanding of the performance of this combination in certain types of patients."

Dr. Wei XU, Vice President of New Drug Biology and Translational Medicine of Innovent, stated: "We were very pleased to release these biomarker results at the ESMO Virtual Congress 2020. MHC-II antigen presentation pathway might predict clinical efficacy of immunotherapy-chemotherapy. This finding could improve our understanding of the mechanism of action of this combination and provide a scientific rationale for future selection of patients who could benefit most."

Dr. Li WANG, Senior VP of Lilly China and Head of Lilly China Drug Development and Medical Affairs Center, stated: "Biomarker exploration is very important to advance cancer immunotherapy. We are very pleased that our discovery of a potential biomarker for immunotherapy will be shared at ESMO. I would like to thank all the investigators, scientists and patients involved in the trial."

About ORIENT-11 Trial

ORIENT-11 is a randomized, double-blind, Phase 3 clinical trial evaluating the efficacy and safety of TYVYT (sintilimab injection) or placebo in combination with ALIMTA (pemetrexed) and platinum chemotherapy as a first-line treatment for advanced or recurrent nonsquamous non-small cell lung cancer (nsqNSCLC) without sensitizing EGFR mutations or ALK rearrangements (ClinicalTrials.gov, NCT03607539). The primary endpoint is progression-free survival (PFS) assessed by Independent Radiographic Review Committee based on RECIST v1.1. The key secondary endpoints include overall survival (OS) and safety profile.

A total of 397 subjects have been enrolled in the ORIENT-11 trial and randomized in a 2:1 ratio to receive either TYVYT (sintilimab injection) 200mg or placebo in combination with ALIMTA (pemetrexed) and platinum chemotherapy every three weeks for up to four cycles, followed by either TYVYT (sintilimab injection) or placebo plus ALIMTA (pemetrexed) maintenance therapy. The subjects will receive treatment until radiographic disease progression, unacceptable toxicity or any other conditions that require treatment discontinuation. Conditional crossover is permitted.

About nsqNSCLC

Lung cancer is a malignancy with the highest morbidity and mortality in China. NSCLC accounts for about 80 to 85 percent of lung cancer. Approximately 70 percent of NSCLC is locally advanced or metastatic at initial diagnosis, resulting in patients with having little to no chance of radical resection. Meanwhile, even after radical surgery, patients have a high chance of recurrence and eventually die from disease progression. About 70 percent of NSCLC in China is nonsquamous subtype and 50 percent of nsqNSCLC is without sensitizing EGFR mutations or ALK rearrangements. These patients do not respond well to targeted therapy and there are limited treatment options available to them.

About TYVYT (Sintilimab Injection)

TYVYT (sintilimab injection), an innovative drug with global quality standards jointly developed in China by Innovent and Lilly, has been granted marketing approval by the NMPA for the treatment of relapsed or refractory classic Hodgkin's lymphoma after two lines or later of systemic chemotherapy, and included in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies. TYVYT (sintilimab injection) is the only PD-1 inhibitor that has been included in the new Catalogue of the National Reimbursement Drug List (NRDL) in November 2019. In April 2020, the NMPA accepted the sNDA for TYVYT (sintilimab injection) in combination with ALIMTA (pemetrexed) and platinum chemotherapy as first-line therapy in nonsquamous non-small cell lung cancer (NSCLC). In May 2020, TYVYT (sintilimab injection) monotherapy met the primary endpoint in the ORIENT-2 study as second-line therapy in patients with advanced or metastatic esophageal squamous cell carcinoma. In August 2020, the NMPA accepted the sNDA for TYVYT (sintilimab injection) in combination with GEMZAR (gemcitabine for injection) and platinum chemotherapy as first-line therapy in squamous NSCLC.

TYVYT (sintilimab injection) is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies for TYVYT (sintilimab injection) to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials. Meanwhile, Innovent is conducting clinical research studies on TYVYT (sintilimab injection) worldwide.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop and commercialize high quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, metabolic, autoimmune and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 23 valuable assets in the fields of cancer, metabolic, autoimmune diseases and other major therapeutic areas, with three products, TYVYT (sintilimab injection), BYVASDA (bevacizumab injection) and SULINNO (adalimumab injection), on market, one asset under NDA review with priority review status, four assets in Phase 3 or pivotal clinical trials, and additional 15 molecules in or close to clinical trials. TYVYT (sintilimab injection) has been the only PD-1 inhibitor included in the NRDL since 2019.

Innovent has built an international team with expertise in cutting-edge biological drug development and commercialization. The company has also entered into strategic collaborations with Eli Lilly and Company, Adimab, Incyte, Alector, MD Anderson Cancer Center, Hanmi and other international partners. For more information, please visit: http://www.innoventbio.com.

About Eli Lilly and Company

Lilly is a global healthcare leader that unites caring with discovery to create medicines to make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at http://www.lilly.com and lilly.com/newsroom.

About Innovent Biologics' strategic collaboration with Eli Lilly and Company

Innovent entered into a strategic collaboration with Lilly focused on biological medicine in March 2015 a groundbreaking partnership between a Chinese pharmaceutical company and a multinational pharmaceutical company. Under the agreement, Innovent and Lilly are co-developing and commercializing oncology medicines, including TYVYT (sintilimab injection) in China. In October 2015, the two companies announced the extension of their existing collaboration to include co-development of three additional oncology antibodies targeting oncology indications. In August 2019, Innovent further entered a licensing agreement with Lilly to develop and commercialize a potentially global best-in-class diabetes medicine in China. Its collaboration with Lilly indicates that Innovent has established a comprehensive level of cooperation between China's innovative pharmaceuticals sector and the international pharmaceuticals sector in fields such as R&D, CMC, clinical development and commercialization. In August, 2020, Lilly and Innovent announced a global expansion of their strategic alliance for TYVYT (sintilimab injection), and Lilly will obtain an exclusive

license for TYVYT for geographies outside of China and plans to pursue registration of TYVYT in the U.S. and other markets.

TYVYT (sintilimab injection, Innovent)

ALIMTA and GEMZAR are trademarks owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates.

Disclaimer:

1. This indication is still under clinical trial, which hasn't been approved in China. 2. Innovent does not recommend any off-label usage.3. For medical and healthcare professional use only.

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SOURCE Innovent Biologics, Inc.

Company Codes: HongKong:1801, OTC-PINK:IVBIY

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Innovent and Lilly Release Biomarker Results of TYVYT (Sintilimab Injection) in Combination with ALIMTA (Pemetrexed) and Platinum Chemotherapy as...

Cell Biology

Sensei Biotherapeutics Reports Early Data from Phase 1/2 Clinical Trial of SNS-301 in Combination with Pembrolizumab in Advanced Head and Neck Cancer…

DetailsCategory: DNA RNA and CellsPublished on Sunday, 20 September 2020 11:04Hits: 162

SNS-301 demonstrated early signals of anti-tumor activity correlated with immune response and tumor infiltration

BOSTON, MA & GAITHERSBURG, MD, USA I September 18, 2020 I Sensei Biotherapeutics, Inc., a clinical-stage biopharmaceutical company developing personalized yet off the shelf immunotherapies for cancer and infectious diseases, announced today results from the Phase 1/2 clinical trial evaluating the safety, efficacy, and immunogenicity of SNS301, a first-in-class bio-engineered, inactivated bacteriophage, in patients with Locally Advanced Unresectable or Metastatic/Recurrent Squamous Cell Carcinoma of the Head and Neck (SCCHN). The data were presented in a poster discussion session at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

Patients with SCCHN often present with immune desert or excluded tumors and only 13-16% of the patients respond to anti PD-1/PDL-1 therapy. Data from the KEYNOTE-012 clinical trial demonstrated that SCCHN patients receiving pembrolizumab alone as 2nd line treatment or later have an objective response rate of 18%, median overall survival of 8 months, and progression-free survival of 2 months. Only 6% of patients with PD-L1 negative disease achieve an objective response to pembrolizumab.

The efficacy of anti-PD-1/PD-L1 is attributed to the presence of infiltrating antigen-specific CD8+ T-cells. Combining anti-PD-1/PD-L1 with agents that generate or expand anti-tumor T-cells, such as vaccines, is critical to increase overall survival of SCCHN patients, said Marie-Louise Fjaellskog, M.D., Ph.D., Chief Medical Officer of Sensei Biotherapeutics. To date, we have observed promising clinical activity that is correlated with immune response for SNS-301, including a partial response in a patient with PD-L1-negative disease. This initial data from 9 patients provides us with the rationale to continue exploring its safety and efficacy in 1st and 2nd line SCCHN patients.

We are excited by the emerging translational data for SNS-301, including - in a patient with a confirmed response - a clear conversion from a poorly inflamed tumor into an inflamed microenvironment, characterized by significant T cell infiltration, and upregulation of PD-L1, said Robert Pierce, M.D., Chief Scientific Officer of Sensei Biotherapeutics. Based on these early promising results, we plan to expand our Immunophage platform to include additional tumor associated antigens and to combine these into bespoke vaccine cocktails based on a patient tumors genetic profile.

The ongoing multi-center Phase 1/2 clinical trial of SNS-301 in combination pembrolizumab is designed to assess the safety, efficacy and immunogenicity of SNS-301 in SCCHN patients that had received anti-PD1/PD-L1 therapy for at least 3 months prior to enrollment with stable disease or unconfirmed progressive disease as their best response upon entry into the study.

Highlights of the Safety, Efficacy and Immunogenicity Data as of July 23, 2020 include:

Based on these data, Sensei plans to enroll all 30 patients for this study. An additional study in neoadjuvant SCCHN patients is planned to begin early next year in combination with Imfimzi (durvalumab).

About SNS-301

SNS-301 is a first-in-class cancer immunotherapy designed to overcome immune tolerance and induce robust and durable antigen-specific humoral and cellular responses. It is a bio-engineered, inactivated bacteriophage virus expressing a fusion protein of native bacteriophage GPD (Glyceraldehyde-3-phosphate dehydrogenase) protein and a selected domain of aspartate -hydroxylase (ASPH). Expression of ASPH is uniquely upregulated in more than 20 different types of cancer and expression levels in various tumors are generally inversely correlated with disease prognosis ASPH signaling is related to cancer cell growth, cell motility and invasiveness, occurs through the Notch pathway, and is implicated in the epithelial to mesenchymal transition (EMT).

About Sensei Biotherapeutics

Sensei Biotherapeutics is a clinical-stage biopharmaceutical company focused on the discovery, development and delivery of precision immunotherapies. The company has developed a unique phage-based platform, ImmunoPhage, that enables the generation of immune activating agents that fully engage the immune system. Its most advanced program, SNS-301, is currently enrolling patients in Phase 2 clinical trials. The company brings together scientific leaders in biology, immunology, and oncology along with a highly experienced management team and scientific advisors. For more information, please visit http://www.senseibio.com.

SOURCE: Sensei Biotherapeutics

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Sensei Biotherapeutics Reports Early Data from Phase 1/2 Clinical Trial of SNS-301 in Combination with Pembrolizumab in Advanced Head and Neck Cancer...

Cell Biology

Enhancing the efficacy of anti-PD-L1 immunotherapy for cancer – News-Medical.net

Reviewed by Emily Henderson, B.Sc.Sep 18 2020

For most people, there is no scarier diagnosis than that of cancer. While treatments including chemotherapy and radiotherapy have been used since the 1940s and late 1800s, respectively, immunotherapy has more recently emerged as a viable and successful approach to cancer treatment. Indeed, evasion of the host immune system is an essential feature of tumorigenesis. Figuring out how cells do this, and disrupting it, to allow the patient's own immune system to eliminate the cancer cells, is the basis of immunotherapy.

In a study published in August 2020 in Nature Cell Biology, a team including researchers from Tokyo Medical and Dental University (TMDU) and Harvard Medical School (HMS) have identified the regulatory mechanisms through which the PD-L1 immune check-point protein dictates the efficacy of anti-PD-L1 immunotherapy.

We already knew that immunotherapies targeting immune-checkpoint inhibitors were somewhat successful in treating some cancer types. However, only a subset of patients achieved long-lasting results."

Naoe Taira Nihira, Co-Author

PD-L1 expression is tightly controlled, and patients with increased PD-L1 expression in tumors are likely to respond well to PD-L1 blockade; however, the reasons why increased PD-L1 expression leads to increased PD-L1 blockade sensitivity have remained unclear. The research team examined a specific kind of PD-L1 modification, called acetylation, and found that removal of this modification allows PD-L1 to enter the nucleus and interact with DNA to regulate the immune response.

Using a variety of advanced molecular, biochemical, and bioinformatics approaches, the researchers examined PD-L1 acetylation, localization, function, and interactions. They found that plasma membrane localized PD-L1 translocates to the nucleus by interacting with transport pathway components. Specifically, by introducing a series of mutations into PD-L1 and expressing different acetyltransferases, they determined that PD-L1 is acetylated by p300 at a specific residue within the cytoplasm called Lys263. Using similar approaches, and protein depletion by short-interfering RNAs, they also discovered that histone deacetylase (HDAC) specifically interacts with and deacetylates PD-L1.

Protein modifications, including acetylation, can affect protein stability, dimerization, or localization. However, when the team reduced the amount of HDAC2 protein in the cells, consequently increasing the acetylation level, there were no observable changes in protein stability or dimerization. Co-author Akira Nakanishi explains: "These results mean that the acetylation and deacetylation of PD-L1 at this residue play a critical role in its nuclear translocation."

In the nucleus, PD-L1 regulates the expression of pro-inflammatory and immune-response-related genes, indicating that PD-L1 could function to regulate the local tumor immune environment to control its sensitivity to immune checkpoint-blockade therapy .

Given the health and economic burdens of cancer worldwide, new treatment approaches with increased efficacy are continually being sought. The results presented by this team indicate that targeting PD-L1 translocation can be used to enhance the efficacy of PD-1/PD-L1 blockade-based immunotherapy approaches.

Source:

Journal reference:

Gao, Y., et al. (2020) Acetylation-dependent regulation of PD-L1 nuclear translocation dictates the efficacy of anti-PD-1 immunotherapy. Nature Cell Biology. doi.org/10.1038/s41556-020-0562-4.

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Enhancing the efficacy of anti-PD-L1 immunotherapy for cancer - News-Medical.net

Cell Biology

Recruiting Faculty in Molecular and Cellular Biology – Nature.com

We invite applications for faculty at the levels of Assistant and Associate Professor within the Department of Molecular and Cellular Biology at Baylor College of Medicine (BCM). BCM is located within the Texas Medical Center in Houston, a premier research and clinical environment.

We are seeking motivated investigators in broad areas of normal and cancer biology, including but not limited to gene regulation, epigenetics, and synthetic biology. BCM offers competitive startup packages and our researchers are supported by outstanding core facilities providing access to dedicated expertise in Genomic, Transcriptomic, and Proteomic Profiling, Advanced and Vital Microscopy, Flow Cytometry, Stem Cell Culture, Live Bioimaging, Metabolomics, and more.

Our Department offers a collegial, collaborative environment and maintains a long-standing tradition of strong support for new faculty. Recruited faculty have the opportunity to join as members of the NCI-designated Dan L Duncan Comprehensive Cancer Center.

BCM is located in the heart of the Texas Medical Center in Houston and is affiliated with surrounding educational institutions, including the University of Texas Medical School, the UT MD Anderson Cancer Center, and Rice University.

Applications received by November 1, 2020 will receive priority.

Please send a cover letter, a CV and a 2-4 page summary of research interests to:

MCB_communications@bcm.edu.

Baylor College of Medicine is an Equal Opportunity/Affirmative Action/Equal Access Employer

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Recruiting Faculty in Molecular and Cellular Biology - Nature.com