What researchers have discovered

In the findings, the researchers wrote that they've identified an epitope on the CD95 receptor that can trigger death in cancer cells.

An epitope is a group of amino acids or chemicals that is typically part of a protein and resides on the surface of a molecule. These epitopes can be recognized by a body's immune system, specifically by antibodies, B-cell receptors, or T-cell receptors, and when the right epitope is recognized, it can cause proteins to activate.

Specifically in the case of CD95 receptors, also known as Fas or "death receptors," once they're activated, they send a signal that causes cells to self-destruct.

"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, an associate professor in the Department of Microbiology and Immunology at UC Davis and senior author of the study.

What this could mean for cancer treatment

Cancer is typically treated with surgery, chemotherapy, and radiotherapy, but if therapy-resistant cancers return, doctors may try immunotherapies, like CAR T-cell-based therapies. T cells are a type of immune cell, and CAR T-cell therapies involve tweaking a patient's T cells with a tumor-targeting antibody.

CAR T-cell therapies have been shown to be effective in leukemia and other blood cancers, but have failed against solid tumors, as tumor microenvironments are effective at keeping T cells and other immune cells away.

"These are often called cold tumors because immune cells simply cannot penetrate the microenvironments to provide a therapeutic effect," Tushir-Singh said. "It doesn't matter how well we engineer the immune receptor activating antibodies and T cells if they cannot get close to the tumor cells. Hence, we need to create spaces so T cells can infiltrate."

However, now that researchers have discovered this epitope, it's possible a drug could be created that would generate a "bystander effect" in conjunction with CAR T-cell therapy, where a cancer cell that lacks the molecule targeted by the CAR T-cell therapy gets destroyed by a drug targeting the new epitope.

"Previous efforts to target this receptor have been unsuccessful," Tushir-Singh said. "But now that we've identified this epitope, there could be a therapeutic path forward to target Fas in tumors."

"We should know a patient's Fas status — particularly the mutations around the discovered epitope — before even considering giving them CAR T," he added. "This is a definitive marker for bystander treatment efficacy of CAR T therapy. But most importantly, this sets the stage to develop antibodies that activate Fas, selectively kill tumor cells, and potentially support CAR T-cell therapy in solid tumors." (UC Davis press release, 10/23; CBS News, 10/26)

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