Engineering Next-Generation CAR T Cells to Outsmart Tumor Resistance

Maria Caterina Rotiroti is a postdoctoral fellow in Dr. Robbie Majzner’s laboratory at the Dana-Farber Cancer Institute. She earned her Ph.D. in 2019 from the University of Milano-Bicocca, Italy, where she conducted her graduate research at Fondazione Tettamanti in Monza, leading projects on CAR T-cell engineering for the treatment of acute myeloid leukemia.

Her research aims to improve the efficacy of Chimeric Antigen Receptor (CAR) T-cell therapy against tumors with heterogeneous antigen expression. CAR T cells are engineered immune cells designed to kill cancer cells by recognizing specific molecules on their surface. While highly effective in some blood cancers, relapses occur in about half of patients. A major limitation is that current CAR T cells lose effectiveness when the target molecule is expressed at low levels, allowing tumor cells to escape immune detection and develop resistance.

To overcome this barrier, Dr. Rotiroti re-engineered the intracellular signaling machinery activated when a CAR binds to its target molecule. This innovation enhances CAR T-cell sensitivity to low antigen levels, enabling them to recognize and eliminate cancer cells that would otherwise evade treatment. Her approach has demonstrated improved tumor control in multiple preclinical models.

The ultimate goal of her work is to develop next-generation CAR T-cell therapies that maintain durable efficacy against tumors with variable antigen expression—paving the way for more resilient and effective cancer immunotherapies.