Dr. Marasco on Engineering CAR T Cells

Wayne A. Marasco, MD, PhD, professor of medicine at Harvard Medical School, and principal investigator of cancer immunology and virology at Dana-Farber Cancer Institute, discusses ways CAR T cells are being engineered to avoid on-target adverse events in solid tumors.

Traditionally, monoclonal antibodies are made with high affinity and high specificity to ensure maximum potency. Conversely, CAR T cells often have to be reverse engineered to decrease their potency.

The affinity of CAR T cells must be downregulated to find a “sweet spot” so that the CAR T cells can recognize a protein that is overexpressed on the tumor cell and not that of a normal cell.