Researchers at the UC Davis Comprehensive Cancer Center have made a significant discovery that could advance cancer treatments. They identified a crucial epitope on the CD95 receptor, also known as Fas, which can activate programmed cell death. By targeting this epitope, researchers believe they can enhance cancer therapies and improve treatment outcomes.
The CD95 receptors, often referred to as “death receptors,” are protein structures found inside cell membranes. When activated, they release a signal that causes cells to self-destruct. The ability to modulate Fas has the potential to extend the benefits of chimeric antigen receptor (CAR) T-cell therapy to solid tumors like ovarian cancer.
Jogender Tushir-Singh, an associate professor in the Department of Medical Microbiology and Immunology and senior author of the study, stated, “We have found the most critical epitope for cytotoxic Fas signaling, as well as CAR T-cell bystander anti-tumor function.”
Previous attempts to target the CD95 receptor have been unsuccessful. However, with the identification of this epitope, researchers believe there is now a therapeutic pathway to effectively target Fas in tumors. This discovery could lead to the development of new drugs that boost death receptor activity, providing a powerful weapon against tumors.
Immunotherapies, such as CAR T-cell-based immune therapies, have shown promise in breaking the cycle of therapy-resistant cancers. However, these treatments have primarily been effective in blood cancers and have failed to provide success against solid tumors. The tumor microenvironment often hinders the effectiveness of CAR T-cell therapies by preventing immune cells from reaching the tumor cells.
By targeting Fas receptors, researchers hope to simultaneously kill tumor cells and create spaces for immune cells to infiltrate solid tumors. Additionally, identifying the mutations around the discovered epitope could lead to new tests that identify which patients will benefit most from CAR T-cell immunotherapy.
Tushir-Singh emphasized the importance of knowing a patient’s Fas status, particularly the mutations around the epitope, before considering CAR T-cell therapy. This information serves as a definitive marker for bystander treatment efficacy, highlighting the potential for selectively killing tumor cells and supporting CAR T-cell therapy in solid tumors.
The study was recently published in the journal Cell Death & Differentiation and was funded by the National Cancer Institute and the U.S. Department of Defense. With further research and development, this breakthrough could revolutionize cancer treatment and provide new hope for patients with solid tumors.