Regulating the fas protein may be the key in overcoming resistance in patients receiving immunotherapy treatment, such as CAR T-cell therapy.
While the advent of immunotherapies like CAR T-cell therapy and checkpoint blockade have forever changed the cancer landscape, many patients who use these treatment modalities relapse. However, recent research in Cancer Discovery may pave the way for more lasting remissions.
The researchers explored the role of FAS, a type of protein that has an important role in mediating cancer grown and the immune system. Its presence causes immunotherapy to find and kill cells that not only possess their specified target, such as CD19, but also surrounding tumor cells that do not have the target. This is caused bystander killing.
In addition to the immunotherapy agent, researchers predict that if another agent is administered to turn off the regulation of RAS, the cancer treatment may become more effective, overcoming the issue of “antigen escape,” when cancer cells evolve and no longer possess the target that the treatment is going after.
“Specifically, by combining immunotherapies with small molecule inhibitors that increase FAS-signaling, which are already being used in the clinic, bystander tumor cell killing may be potentiated and eliminate antigen-loss variants from heterogenous tumors,” said Joshua Brody, MD, Director of the Lymphoma Immunotherapy Program at The Tisch Cancer Institute at Mount Sinai, in a statement.
The study involved patients with non-Hodgkin lymphoma receiving CAR T-cell therapy. Researchers found that the levels of FAS found in tumors had an effect on both the patients’ response to the drugs as well as long-term survival — those with significantly elevated FAS levels had more durable responses to therapy.
Brody explained that these exciting findings may lay the groundwork for more research in the future.
“This study should engender many clinical trials solving the common weakness of immunotherapies—antigen escape and relapse,” he said.