Scientists devise strategies to counteract T cell exhaustion in CAR T cancer therapies

Medical Xpress | February 27, 2019

A growing number of cancer patients are being offered a promising new treatment called CAR T cell therapy. In this therapy, a patients' own T cells are removed and genetically engineered to better recognize cancer cells. The cells are then returned to the patient's body, where they mount an immune response to destroy cancer. CAR T-cell therapies have saved lives in patients with blood cancers, but there has been a downside: T cells that enter solid tumors can stop working due to a phenomenon called T cell exhaustion. Now scientists at the La Jolla Institute of Immunology (LJI) have found a way of counteracting T cell exhaustion and making CAR T cell therapies more effective. Their new study shows that a family of proteins, called Nr4a transcription factors, have a prominent role in regulating the genes associated with T cell exhaustion. Using a mouse model, the scientists demonstrated that treating mice with CAR T cells lacking these Nr4a transcription factors led to smaller tumors and better survival. The study, published February 27, 2019, in the journal Nature, was led by LJI researcher Anjana Rao, Ph.D., a professor in the Division of Signaling and Gene Expression. Previous studies from her lab showed that another family of transcription factors, known as NFAT, turned on Nr4a proteins in T cells that entered tumors. In 2017, the Rao lab co-led a study with LJI researcher Patrick Hogan, Ph.D., that measured "exhaustion markers" in T cells in a mouse model of melanoma. Their analysis suggested that NFAT and Nr4a proteins contribute to exhaustion in T cells fighting cancer.

Spotlight

Learn how stem cells help regenerate cartilage and slow down degenerative arthritis.

Spotlight

Learn how stem cells help regenerate cartilage and slow down degenerative arthritis.

Related News

MEDICAL

Mogrify announces Exploratory Research Collaboration with MRC Laboratory of Molecular Biology

Mogrify | January 11, 2021

Mogrify Limited (Mogrify®), a UK organization expecting to change the advancement of ex vivo cell therapies and pioneer the field of in vivo reconstructing treatments, and the MRC Laboratory of Molecular Biology (LMB), a top notch research lab committed to understanding significant natural cycles at the sub-atomic level, today reported an exploratory examination cooperation. The venture intends to create novel protein articulation frameworks by utilizing late advances in direct cell reconstructing to help improve the creation of proteins which are not delivered adequately well in existing articulation frameworks. The MOGRIFY® technology will be applied to foresee mixes of record variables to incite trans-separation starting with one cell type then onto the next. The subsequent objective cell types could give analysts improved admittance to significant proteins found in human cell types that are hard to get and take into consideration more efficient protein production. Mogrify will get admittance to any licensed innovation and skill created during the undertaking, further empowering the commercialization of the innovation in regions of remedial worth. This coordinated effort is a development of the Company's relationship with the MRC LMB and follows the declaration in December 2020 that it had made sure about a restrictive permit from the MRC LMB to an upgraded form of MOGRIFY technology empowering more precise record factor expectations and improved cell transformation viability. In the interest of the MRC, the clinical exploration noble cause LifeArc encouraged the restrictive permit of the new form of Mogrify's center reconstructing stage, and together arranged the legitimate structure to empower a fruitful cooperation between the MRC and Mogrify.

Read More

MEDTECH

FDA Grants ILiAD Biotechnologies Fast Track Designation for Next Generation Pertussis Vaccine BPZE1

ILiAD Biotechnologies | January 04, 2022

ILiAD Biotechnologies, a late stage biotech development company focused on global eradication of disease due to Bordetella pertussis, announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to BPZE1, a next generation vaccine for active booster immunization against pertussis. BPZE1 is the most advanced next generation pertussis vaccine currently in clinical development. Developed in the laboratory of Camille Locht, PhD, at the Institut Pasteur de Lille and French National Institute of Health and Medical research BPZE1 is a live-attenuated intranasal vaccine designed to overcome deficiencies of current pertussis vaccines, including poor durability of protection and failure to prevent nasopharyngeal Bordetella pertussis infections that lead to escape mutants and transmission to vulnerable infants. Four clinical trials studying BPZE1 in healthy adults have been completed to date, including positive topline results from a 300-participant adult Phase 2b trial demonstrating that BPZE1 induced durable mucosal immunity and reduced nasal colonization — two key factors necessary for the prevention of transmission and reduction of epidemic pertussis cycles. Earlier this month, the Company also announced initiation and enrollment of the first participants in the BPZE1 SUPER Trial (Standing Up to PERtussis) – the fifth clinical BPZE1 study and the first study in school-age children. Section 506(b) of the FD&C Act provides for the designation of a drug as a Fast Track product “…if it is intended, whether alone or in combination with one or more other drugs, for the treatment of a serious or life-threatening disease or condition, and it demonstrates the potential to address unmet medical needs for such a disease or condition.” Fast Track provides opportunities for frequent Company interactions with the FDA and the potential for accelerated approval and priority review. “We are pleased that the FDA is aligned with ILiAD’s position that there is an unmet clinical need for a more effective pertussis vaccine and that the evidence to date supports the potential for BPZE1 to address the major gaps in protection against pertussis. We look forward to continuing to work with the FDA and other global Regulatory Agencies to further clinical development of BPZE1 and to safely and efficiently bring BPZE1 to US and global markets.” Dr. Keith Rubin, Chief Executive Officer of ILiAD. Dr. Rubin About Pertussis Pertussis is a life-threatening disease caused by the highly contagious respiratory bacterium Bordetella pertussis. According to U.S. Centers for Disease Control and Prevention, each year pertussis affects approximately 16 million people globally, accounting for nearly 200,000 deaths. Although estimated global vaccination coverage is 84%, current vaccines have failed to control epidemics. In addition, current vaccines do not fully protect infants under age 6 months, since immunization requires multiple injections, usually at 2, 4 and 6 months. About BPZE1 BPZE1 is a next-generation live-attenuated pertussis vaccine designed to induce comprehensive and durable protection against B. pertussis infection and disease. BPZE1 is being developed to block B. pertussis from colonizing adult and adolescent nasal passages, to protect adults and adolescents from whooping cough, and to potentially prevent transmission, including transmission to infants. While ILiAD is currently focused on developing a vaccine to directly protect adults and adolescents and to indirectly protect vulnerable infants, future development aims to immunize neonates directly. About Fast Track Designation Fast Track Designation by the U.S. FDA is a process designed to facilitate the development and expedite the review of investigational products to treat serious conditions and fill an unmet medical need, with the intent of getting important new products to the population in an expedited manner. Specifically, Fast Track Designation provides the option of licensure via the accelerated approval pathway, which allows licensure based on surrogate endpoints. Additionally, Fast Track designation facilitates meetings with the FDA to discuss all aspects of development to support licensure and provides the opportunity to submit sections of a BLA on a rolling basis as data become available. This permits the FDA to review modules of the BLA as they are received instead of waiting for the entire BLA submission. Priority review is an additional benefit that may potentially be available for BPZE1 as part of the Fast Track designation. About ILiAD Biotechnologies, LLC ILiAD Biotechnologies is a privately held, clinical stage biotechnology company dedicated to the prevention and treatment of human disease caused by Bordetella pertussis. The company is developing and acquiring key technologies, working with leading scientists to overcome the limitations of current vaccines, investigating the impact of B. pertussis in a range of human disease, and is focused on validating its proprietary vaccines in human clinical trials.

Read More

MEDICAL

Sotira Announces the Successful Completion of Second Phase of Pre-Clinical Testing for COVID-19 Therapeutic and Vaccine-Alternative

Sotira | November 25, 2020

Sotira, the Phoenix based biotech organization, is pleased to report the successful finish of the second period of pre-clinical testing for its COVID-19 therapeutic and vaccine-alternative, KEPTIDE™ COVID, confirming that this cutting-edge molecular therapy completely prevented of SARS-CoV2 in the lungs and kidney. These mice are viewed as a best quality level preclinical model to study COVID-19 on the grounds that the mice express human ACE2, the receptor utilized by the virus to gain entry to cells. The Sotira scientific group additionally found that the intranasal treatment of KEPTIDE™, 30 minutes before viral organization, secures wounds in lungs and kidney, yet additionally forestalls intense demise reaction in these humanized mice. Founded by James Keating, Sotira is a pharmaceutical and therapeutic company dedicated to developing cutting-edge molecular therapy to treat and prevent diseases. Led by its proprietary, patent-pending KEPTIDE™ technology, Sotira specializes in pharmaceutical preparations and substances for the treatment of infectious diseases, blood disorders, pain, inflammation, sepsis, alopecia, obesity, cognitive disorders, respiratory diseases, asthma, and of course the prevention of SARS-CoV2 (aka COVID-19).

Read More