Researchers from the Institute of Human Virology (IHV), University of Maryland School of Medicine (UMSOM) have proposed a new theory to improve both the efficacy and safety of immunotherapy drugs. The theory calls for a new drug design with an emphasis on side-effect prevention while enabling higher doses of the drug to be administered.
Typically immunotherapy treatments for cancer are “checkpoint blockade” immunotherapy (CBI) drugs designed to block a “checkpoint” molecule that rests on the surface of certain immune cells. Such a block is needed to help the body’s immune cells recognize and attack tumor cells as foreign.
Checkpoints typically keep the immune system from attacking healthy cells as foreign invaders in healthy tissues however. Consequently blocking them can trigger severe autoimmune reactions in a patient where the body attacks its own healthy tissues and cells. In order to prevent these dangerous autoimmune reactions, physicians often must limit the doses administered to a patient, which in turn limits the effectiveness of these drugs.
The Study Theory
The new theory was developed to lead to more effectively designed immunotherapy treatments targeting the CTLA-4 immune checkpoint. Immunotherapy drugs should not be designed to inactivate the CTLA-4 immune checkpoint on the immune T cells that protect against autoimmune diseases. Rather, these drugs should be designed to selectively deplete the regulatory T cells in the tumors while preserving the checkpoints on healthy T cells. This, the study authors posit, could render the drugs less toxic and enable oncologists to administer the therapy at higher doses.
Preclinical Study on Mice Model
The researchers’ theory is based on extensive research they conducted including a published study in August 2019 in the journal Cell Research. They and IHV colleagues tested a new therapy that selectively targets CTLA-4, a checkpoint on T cells, and uncovered that without affecting CTLA-4 function outside the tumors, it selectively targets the CTLA-4, a checkpoint on T cells, and selectively destroyed the regulatory T cells within the tumor. The team found that this approach, in a mouse model, was much less toxic to the animals and even more effective at destroying the tumor cells reported the University of Maryland, Baltimore.
Apparently two additional studies, published in 2018 in the journal Cell Research, which were awarded the 2018 Sanofi-Cell Research outstanding paper award—also offered evidence to support this new theory. Researchers involved in these efforts included:
· Xuexiang Du, PhD, research associate of surgery, IHV
· Yan Zhang, PhD, research associate of surgery, HIV
· Mingyue Liu, PhD, post doc fellow, IHV
· Fei Tang, PhD, research associate of surgery, IHV
The study was funded by an NIH grant (AI64350) and (CA227671), Melanoma Research Alliances, and a grant from Oncolmmune, Inc.
Note on Oncolmmune Inc
Oncolmmune Inc. is a new venture, of which Dr Liu and Dr. Zheng are co-founders and have equity interests. Based in Rockville, Maryland, OncoImmune is a privately-held, clinical-stage biopharmaceutical company that is actively engaged in the discovery and development of novel biopharmaceuticals for the treatment of cancer and autoimmune disease.
The Institute of Human Virology
Formed in 1996 as a partnership between the State of Maryland, the City of Baltimore, the University System of Maryland and the University of Maryland Medical System, IHV is an institute of the University of Maryland School of Medicine and is home to some of the most globally-recognized and world-renowned experts in all of virology. This institution combines the disciplines of basic research, epidemiology and clinical research in a concerted effort to accelerate the discovery of diagnostics and therapeutics for a wide variety of chronic and deadly viral and immune disorders—most notably, HIV.
Yang Liu, MD, professor of surgery and director, Division of Immunotherapy, IHV
Pan Zheng, MD, PhD, professor of surgery, Division of Immunotherapy, IHVSource: University of Maryland