Dr. Brody on Modulating Fas Signaling to Prevent Relapse in Hematologic Malignancies

Joshua Brody, MD, director, Lymphoma program, Icahn School of Medicine, Mount Sinai Hospital, discusses Fas and its impact on bystander killing in patients with non-Hodgkin lymphoma.

Tumor cells that express Fas are sensitive to bystander killing, while those that don't express Fas are completely resistant to bystander killing, says Brody. To date, there’s a great deal of information available on Fas. For example, it has been discovered that, with FDA-approved small molecule inhibitors such as BCL-2, HDAC, and IAP inhibitors, Fas signaling in tumor cells can be increased, Brody explains.

Furthermore, by inhibiting Fas signaling regulators, bystander killing can be increased and antigen-negative tumor cells can be destroyed, Brody explains. Interestingly, investigators believe that the geographic targeting of antigen loss tumor cells may be a way to avoid antigen loss. This would be an extraordinarily practical and simple method, Brody says.

Furthermore, patients who were treated with CAR T-cell therapy in the ZUMA-1 trial, a single-arm, multicenter, registrational trial that was conducted at 22 sites in the USA and Israel, were more likely to respond to therapy when they had high levels of Fas in their tumors. These patients were also much more likely to survive 1 year after receiving the CD19-directed CAR T-cell therapy, Brody explains.

Numerous ongoing trials continue to show the importance of Fas signaling receptors. Investigators believe that, by modulating Fas signaling, they may be able to prevent patients with hematologic malignancies from relapsing, Brody concludes.