Dr. Wang on Combatting CAR T-Cell Therapy Resistance in MCL

Michael Wang, MD, professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, discusses resistance to CAR T-cell therapy and the next steps to overcoming this challenge in treatment for mantle cell lymphoma (MCL).

CD19-targeted CAR T-cell therapy can put some patients with MCL into long-term remission, but most will relapse, according to Wang. Therefore, there need to be ways to overcome CAR T-cell resistance, which might be due to the loss of an antigen or because the parallel pathways are overly activated, explains Wang. If CD19 is lost, new targets need to be found. One method, Wang says, is attacking 2 targets at the same time to overcome some of the resistance by loss of 1 target. Currently, MCL treatment does not commercially include CAR T cells.

In an era of precision medicine, DNA/RNA epigenetic mutations could be used to wield the discrete mechanism of resistance in each patient and then target this pathway to overcome resistance in a personalized fashion, concludes Wang.