The Struggle Is Real for CAR T-Cell Therapy: Kerry Rogers, MD

Chimeric antigen receptor (CAR) T-cell therapy has transformed outcomes in several blood cancers, but its success is far from uniform. According to Kerry Rogers, MD, an associate professor at The James—The Ohio State University Comprehensive Cancer Center, the differences come down to a handful of biological factors that vary widely from one disease to the next.

Having the Right Target Matters Most

The first requirement, Rogers explained, is a reliable target. Diseases with well-established monoclonal antibody targets tend to be the ones where CAR T-cell therapy thrives. In acute lymphoblastic leukemia (ALL), blinatumomab targets CD19; in diffuse large B-cell lymphoma (DLBCL) and other B-cell lymphomas, CD20-directed antibodies are standard. CD19, in particular, is expressed broadly on B cells, giving CAR T-cell therapy developers a target that can eliminate the cancer without devastating consequences elsewhere in the body. By contrast, Rogers noted, acute myeloid leukemia lacks a marker specific enough to hit cancer cells without also destroying most of a patient’s bone marrow. CD19, in particular, is expressed broadly on B cells, giving CAR T-cell therapy developers a target that can eliminate the cancer without devastating consequences elsewhere in the body. By contrast, Rogers noted, acute myeloid leukemia lacks a marker specific enough to hit cancer cells without also destroying most of a patient's bone marrow.

Why Is Manufacturing a Major Hurdle?

Even with a good target, the T cells must be manufacturable. Rogers, who focuses on chronic lymphocytic leukemia (CLL), said manufacturing was historically a significant barrier in that disease, with success rates far lower in ALL or DLBCL. Improvements in manufacturing techniques, treatment with Bruton tyrosine kinase (BTK) inhibitors to improve T-cell health, and treating patients earlier with less prior chemotherapy have all helped raise CLL manufacturing success rates, with newer lisocabtagene maraleucel (liso-cel; Breyanzi; Bristol Myers Squibb) trials seeing failure in fewer than 5% of patients.

However, even successfully manufactured T cells must expand and function effectively once infused. Rogers pointed to the immune-evasive nature of certain cancers, along with broader immune dysregulation, as key variables. This is especially relevant in lymphomas, which arise from immune system cells and can create an environment less hospitable to CAR T-cell expansion.

Together, these factors—target availability, manufacturing feasibility, and immune environment—help explain why CAR T-cell therapy has become a cornerstone treatment for some blood cancers while remaining an elusive option for others.