Researchers Identify “Switch” to Activate Cancer Cell Death

Antigen-positive tumor cell (blue, left) is a direct target of CAR T-cells (light red) due to high-affinity antibody-antigen contacts. On the contrary, an antigen-negative tumor cell (light golden, right) is killed by Fas-mediated "bystander" killing. Cancer patients with high Fas-expression are expected to respond significantly better to immunotherapies.
A research team from the UC Davis Comprehensive Cancer Center has identified a crucial epitope (a protein section that can activate the larger protein) on the CD95 receptor that can cause cells to die. This new ability to trigger programmed cell death could open the door for improved cancer treatments. The findings were published October 14, 2023 in the Nature journal Cell Death & Differentiation. CD95 receptors, also known as Fas, are called death receptors. These protein receptors reside on cell membranes. When activated, they release   a signal that causes the cells to self-destruct. Modulating Fas may also extend the benefits of chimeric antigen receptor (CAR) T-cell therapy to solid tumors like ovarian cancer. “We have found the most critical epitope for cytotoxic Fas signaling, as well as CAR T-cell bystander anti-tumor function,” said Jogender Tushir-Singh, PhD, an Associate Professor in the Department of Medical Microbiology and Immunology and senior author of the study. “Previous efforts to target this receptor have been unsuccessful. But now that we’ve identified this epitope, there could be a therapeutic path forward to target Fas in tumors,” Dr. Tushir-Singh said. The open-access article is titled “Characterizing the Regulatory Fas (CD95) Epitope Critical for Agonist Antibody Targeting and CAR-T Bystander Function in Ovarian Cancer.”                                                                 
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