Unveiling the Impact of Antigen History on CAR-T Cell Function

Research from the University of Colorado Anschutz Medical Campus shows that CAR-T cells—engineered to fight cancer—can retain memories of past antigen encounters, potentially improving treatment precision.

Published in Nature Immunology, the study highlights differences between memory cells (those with past antigen exposure) and naïve cells (without prior exposure). Memory cells were effective at destroying cancer but quickly became exhausted, while naïve cells showed robust growth and resistance to fatigue.

“Unlike most drugs, CAR-T cell products are not uniform. We know variability exists, but we’re only beginning to understand its nature. The surprising finding here was how durably past interactions with antigens are imprinted on these cells,” said Terry Fry, the study’s senior author and professor at the University of Colorado.

Targeting genes like RUNX2 enhanced the function of naïve cells, making them more effective and resistant to exhaustion. “These epigenetic differences allow us to identify genes that can be manipulated to enhance function,” added lead author Kole DeGolier, PhD.

The findings could guide more precise CAR-T cell engineering, improving cancer treatment while reducing side effects. “Understanding these differences can guide the development of approaches to rationally manipulate specific cellular attributes,” the authors noted.