Researchers identify CTLA-4 response marker

European Biotechnology | September 16, 2019

The research team headed by Simon Heideger and Hendrick Poeck from Technical University of Munich together with colleagues from Memorial Sloan Kettering Cancer Center, New York, provided new evidence that activation of the RNA-sensing molecule RIG-I on tumour cells  is critical for responsiveness to checkpoint blockade. As only 30% of cancer patients respond to checkpoint inhibitor therapy while some show severe side effects, RIG-I expression might identify the patients benefiting most from this sort of cancer immunotherapy. Secondly, therapies, which combine a checkpoint blocker and a RIG-I agonist, might help boost the effectiveness of checkpoint inhibitors and, thus, enhance the response rate to cancer immunotherapy. Specifically, Heideger et al. provided preclinical evidence that a combination of a RIG-I oligonucleotide agonist and a CTLA-4 checkpoint blocker prolonged survival in several preclinical cancer models. Furthermore, high expression of DDX58, the gene encoding RIG-1, in cell cultures made from samples of melanoma patients predicted improved survival under CTLA-4 therapy. The authors suggest that testing tumour cells from humans for susceptibility to RIG-I-driven cell death might serve as a biomarker to predict treatment outcomes of CTLA-4 checkpoint inhibition.

Spotlight

Sesquizygotic multiple pregnancies is an exceptional intermediate between monozygotic and dizygotic twinning. We report a monochorionic twin pregnancy with fetal sex discordance. Genotyping of amniotic fluid from each sac showed that the twins were maternally identical but chimerically shared 78% of their paternal genome

Spotlight

Sesquizygotic multiple pregnancies is an exceptional intermediate between monozygotic and dizygotic twinning. We report a monochorionic twin pregnancy with fetal sex discordance. Genotyping of amniotic fluid from each sac showed that the twins were maternally identical but chimerically shared 78% of their paternal genome

Related News

INDUSTRIAL IMPACT

Kane Biotech Announces New Collaboration Agreements for Prosthetic Joint Infection, expanding its DispersinB® applications

Kane Biotech Inc. | February 11, 2022

Kane Biotech Inc. announces that it has signed collaboration agreements with Dr. James Doub, MD, Assistant Professor of Medicine, University of Maryland School of Medicine’s Institute of Human Virology, and the University of Texas Medical Branch (UTMB) to study the use of DispersinB® with Prosthetic Joint Infection (PJI) patients. The group is securing funding from the National Institutes of Health (NIH) for pre-clinical work to be done by Josh Wenke, a Professor in the Department of Orthopedic Surgery and Rehabilitation at UTMB. PJI’s are one of the most serious complications of joint replacement surgery. Conservative estimates are that approximately 1–2% of all prostheses will become infected over the life of the implant [1]. The financial burden of treating these infections is staggering. It is estimated that they will cost the US healthcare system $1.62 billion in 2020 [1]. In addition, patients have significant morbidity and mortality as a direct result of our current medical and surgical management to treat these infections [2]. In one study, the five-year mortality for prosthetic joint infections is over 20% [2]. “These collaborations are of utmost importance given our shared strategies for managing complex musculoskeletal infections and finding cures for the debilitating morbidity associated with PJI. We are highly optimistic of advancing this field scientifically and clinically for the benefit of patients across the globe” Marc Edwards, CEO of Kane Biotech “The Institute of Human Virology has been testing the use of bacteriophage therapeutics in treating recalcitrant PJIs with some early signals of success,” explained Dr. Doub, who is also Director of Infectious Diseases Ambulatory Practice at the University of Maryland Medicine Center. “However, DispersinB®, has properties that bacteriophages do not have which include superior application as a preventative therapeutic, broader spectrum of activity, and a much easier regulatory (FDA) path.” Dr. Doub is a consultant for Kane Biotech. Dr. Nanda Yakandawala, Vice President of Research and Development at Kane, in collaboration with Dr. Doub and Josh Wenke, Ph. D, recently submitted a R-21 grant application to NIH to fund pre-clinical work to be performed by Dr. Wenke. About University of Texas Medical Department Established in 1891 as the University of Texas Medical Department, UTMB was the nation's first public medical school and hospital under unified leadership and has evolved into a modern academic health science center with multiple campus locations and almost 1,000 faculty members educating approximately 3,500 students. Since the beginning, UTMB has been at the forefront of medical research, with researchers studying the viruses common to a sub-tropical island climate. Today, our world-renowned investigators generate a portfolio exceeding $160 million, and work in state-of-the-art laboratories developing diagnostic tools, cures and vaccines to benefit the global community. About Kane Biotech Kane Biotech is a biotechnology company engaged in the research, development, and commercialization of technologies and products that prevent and remove microbial biofilms. The company has a portfolio of biotechnologies, intellectual property (81 patents and patents pending, trade secrets, and trademarks) and products developed by the company's own biofilm research expertise and acquired from leading research institutions. StrixNB™, DispersinB®, Aledex™, bluestem™, bluestem®, silkstem™, goldstem™, coactiv+™, coactiv+®, DermaKB™ and DermaKB Biofilm™ are trademarks of Kane Biotech Inc.

Read More

MEDICAL

Be Bio and Resilience Announce Strategic Collaboration to Manufacture Engineered B Cells, a New Class of Cellular Medicines

Be Bio | May 20, 2022

Be Biopharma, Inc. (“Be Bio”) and National Resilience, Inc. (Resilience) today announced a strategic collaboration to advance initial programs in Be Bio’s rare disease pipeline. Be Bio’s proprietary engineered B Cell Medicines (BeCM) platform is harnessing the power of the human B cell to create a new class of autologous and allogeneic cellular medicines that durably and redosably produce therapeutic proteins in vivo without toxic pre-conditioning. The two companies are investing to drive innovation and reliability in cell therapy manufacturing, a critical success factor for broad and meaningful patient impact. As part of this unique partnership, Resilience will dedicate personnel solely to produce and supply Good Manufacturing Practices (GMP)-grade viral vector and cell therapy drug product for the initial programs in Be Bio’s rare disease pipeline. Through a creative cost and risk-sharing model, Resilience will be responsible for manufacturing costs and receive potential future milestones and royalties. Over the past year, Be Bio has built a strong foundation with our BeCM platform, pipeline, team, and recent $130 million financing. Manufacturing is critical to rapidly progress our BeCMs to the clinic and we have built non-GMP manufacturing capabilities in our Cambridge facility. This deal allows us to drive GMP manufacturing with an outstanding partner, and in a capital efficient manner, Resilience’s broad manufacturing capabilities, strong collaborative spirit and dedicated resources to our platform, make them an ideal partner for our BeCM programs.” Joanne Smith-Farrell, Ph.D., Chief Executive Officer at Be Bio. Resilience will lead clinical GMP manufacturing of both the viral vector and the cell therapy drug product for Be Bio’s initial rare disease programs to support first-in-human clinical trials. Resilience will apply its pioneering bioprocessing solutions and network of cell therapy sites, including facilities in Research Triangle Park, NC, Philadelphia, PA, Waltham, MA and Marlborough, MA to conduct the work. This collaboration shows our excitement for the promising science of Be Bio’s proprietary BeCM platforms, and our confidence in their expertise to deliver transformative cell therapies, By working alongside Be Bio early in the drug development process, we aim to accelerate the development of their B cell medicines with the potential to unlock a pipeline of product candidates across a variety of serious diseases.” Rahul Singhvi, Sc.D., Chief Executive Officer of Resilience. About B Cells – A New Class of Cellular Medicines Imagine what could “Be?” In nature, a single B cell engrafts in the bone marrow and can produce thousands of proteins per second at constant levels over decades. B cells are nature’s exquisite medicine factories, manufacturing proteins to fight disease and maintain health. Unleashing the power of B cells is driving a new class of cellular medicines – Engineered B Cell Medicines (BeCM). BeCMs have the potential to be durable, allogeneic, redosable and administered without toxic conditioning. The promise of BeCMs could transform therapeutic biologics with broad application — across protein classes, patient populations and therapeutic areas. About Be Biopharma Be Biopharma (“Be Bio”) is pioneering Engineered B Cell Medicines (BeCM) to dramatically improve patients’ lives who are living with cancer, rare diseases and other serious conditions. With eyes locked on the patient, our team of purpose-driven scientists, technologists, manufacturing experts and business builders collaborate to create a bold new class of cell therapies. Be Bio was founded in October 2020 by Longwood Fund and B cell engineering pioneers David Rawlings, M.D., and Richard James, Ph.D. from Seattle Children’s Research Institute. Be Bio is backed by ARCH Venture Partners, Atlas Venture, RA Capital Management, Alta Partners, Longwood Fund, Bristol Myers Squibb and Takeda Ventures. Since our founding, Be Bio’s investors have committed over $180 million to enable the Company to re-imagine medicine based on the power of B cell therapy. About Resilience Resilience is a technology-focused biomanufacturing company dedicated to broadening access to complex medicines. Founded in 2020, the company is building a sustainable network of high-tech, end-to-end manufacturing solutions to ensure the treatments of today and tomorrow can be made quickly, safely, and at scale. Resilience seeks to free its partners to focus on the discoveries that improve patients’ lives by continuously advancing the science of biopharmaceutical manufacturing and development.

Read More

INDUSTRIAL IMPACT

Legend Biotech Achieves Milestone Payments in BCMA CAR-T Collaboration with Janssen

Legend Biotech Corporation | February 14, 2022

Legend Biotech Corporation, a global, clinical-stage biotechnology company developing and manufacturing novel therapies, has achieved two milestones under its collaboration agreement with Janssen Biotech, Inc. for ciltacabtagene autoleucel (cilta-cel), resulting in aggregate payments to Legend Biotech of $50 million. Cilta-cel is a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy. Legend Biotech entered into the agreement with Janssen to develop, manufacture and commercialize cilta-cel for the treatment of multiple myeloma. Under the agreement, Legend Biotech received an upfront payment of $350 million and is entitled to receive additional payments upon achievement of landmarks for development, production performance, regulatory and sales. The global agreement specifies a 50-50 cost and profit-sharing agreement in all markets, excluding Greater China, where the split is 70 percent for Legend and 30 percent for Janssen. Including the payments announced above, Legend has achieved $250 million in milestone payments during the collaboration. About Cilta-cel Cilta-cel is an investigational chimeric antigen receptor T cell (CAR-T) therapy, formerly identified as JNJ-4528 in the United States and Europe and LCAR-B38M CAR-T cells in China, that is being studied in a comprehensive clinical development program for the treatment of patients with relapsed or refractory multiple myeloma and in earlier lines of treatment. The design consists of a structurally differentiated CAR-T with two BCMA-targeting single domain antibodies. In addition to a Breakthrough Therapy Designation (BTD) granted in the United States in December 2019, cilta-cel received a Priority Medicines (PRiME) designation from the European Commission in April 2019, and a BTD in China in August 2020. In addition, Orphan Drug Designation was granted for cilta-cel by the U.S. Food and Drug Administration (FDA) in February 2019, and by the European Commission in February 2020. A Biologics License Application seeking approval of cilta-cel was submitted to the U.S. FDA and a Marketing Authorization Application was submitted to the European Medicines Agency. About Legend Biotech Legend Biotech is a global, clinical-stage biotechnology company dedicated to treating, and one day curing, life-threatening diseases. Headquartered in Somerset, New Jersey, we are developing advanced cell therapies across a diverse array of technology platforms, including autologous and allogenic chimeric antigen receptor T-cell, T-cell receptor (TCR-T), and natural killer (NK) cell-based immunotherapy. From our three R&D sites around the world, we apply these innovative technologies to pursue the discovery of safe, efficacious and cutting-edge therapeutics for patients worldwide. We are currently engaged in a strategic collaboration to develop and commercialize our lead product candidate, ciltacabtagene autoleucel, an investigational BCMA-targeted CAR-T cell therapy for patients living with multiple myeloma. Applications seeking approval of cilta-cel for the treatment of patients with RRMM are currently under regulatory review by several health authorities around the world, including the U.S. Food and Drug Administration and the European Medicines Agency.

Read More