Dr. Brody on the Challenges of Antigen Escape in MCL

Joshua Brody, MD, director, Lymphoma program, Icahn School of Medicine, Mount Sinai Hospital, discusses the challenges of mitigating antigen escape in mantle cell lymphoma (MCL).

Antigen escape with CAR T-cell therapy is a common mechanism of resistance that causes the loss or downregulation of the target antigen on the cancer cell.

If the cell loses CD19, a CD22-directed CAR T-cell product could potentially be used, Brody explains. However, the ultimate goal is to prevent antigen escape rather than treat it with an alternative therapy.

Additionally, sometimes the cell can lose multiple differentiation antigens in aggregate, says Brody. For example, if a cell loses CD19, CD20, and CD22, dual-specific CAR T-cell therapies will be unable to target the antigen.

Currently, ongoing research is attempting to mitigate antigen escape by targeting the antigen-positive cells that surround the antigen-negative cell, Brody says. This approach could potentiate the bystander-killing effect of the therapy.

Antigen escape also provides potential rationale to investigate combination therapies with CAR T-cell therapy, bispecific antibodies, and checkpoint inhibitors, concludes Brody.