New CAR T study in MM aims at triple receptor targeting

The BAFF CAR T Phase 1 clinical trial is investigating a new way to deliver chimeric antigen receptor (CAR) T cell therapy to its intended targets on two fronts: by specifically targeting three cell receptors – BAFF receptors, B cell maturation antigen (BCMA) and transmembrane activator and CAML interactor (TACI) – as opposed to the typical single receptor (CD19), and by electroporation instead of administration via lentiviral vectors. The American Journal of Managed Care® spoke with lead investigator Dr. Leland Metheny about the goals of the study and how targeting 3 receptors versus 1 receptor works.

Metheny is a hematologist and oncologist at University Hospitals Seidman Cancer Center and an assistant professor of medicine at Case Western Reserve University School of Medicine in Cleveland, Ohio.

Transcript

What primary and secondary outcomes are you interested in in the BAFF CAR T clinical trial?

The BAFF CAR T Phase 1 clinical trial is, of course, a Phase 1 trial. We're looking at safety, that's the primary outcome. In addition, we want to look at efficacy and duration of efficacy, so how long we can impact progression-free survival in patients with multiple myeloma. And there are some correlating outcomes that we're looking at: DNA integration, persistence of the CAR T cells in patients, and immunological endpoints, focusing on how long the immunosuppression lasts in people and things like that.

Can you explain how your triple objective approach works?

This CAR-T cell targets 3 receptors on mature B cells and plasma cells. The typical CAR-T cell recognizes 1 of these. One of the most common is CD19 and is used to treat certain lymphomas. Another receptor used in multiple myeloma is BCMA; this is a target for many CAR-T cells in multiple myeloma.

This target is a ligand-based target, meaning there are receptors on the cell surface that attach to ligands, and this CAR-T cell acts as a sort of artificial ligand and attaches to 3 receptors on cell surfaces. One is the BAFF receptor, one is BCMA, and one is TACI. The benefit of being able to recognize the cells with these receptors, attach to them, and then attack them is that it is much harder for a cancer cell with these 3 receptors – like certain types of lymphoma and myeloma – to downregulate all 3 receptors than just one. So it is less likely to cause immune escape in this context.