Where are we now? The promises and pitfalls of solid tumor CAR-T therapy

Erika Sloan from the global consulting firm CRA and Siddharth Arun, a former consulting associate at CRA, discuss the future of innovation of CAR-T therapies in the solid tumor space and challenges that drug manufacturers must address to be successful in this Expert View Column.

CAR T-cell therapy (CAR-T) has emerged as a therapeutic option with the ability to infiltrate and modulate the tumor microenvironment and control tumor growth. While normal T-cells with effector features have difficulty infiltrating the complex tumor microenvironment, ex vivo reprogramming of a patient’s own T-cells with a chimeric antigen receptor (CAR) enables the targeting of specific tumor antigens and the appropriate direction of immune responses. Given the reprogramming of a patient’s T-cells, CAR-T cells are advantageous in that they have unique specificity and can control cancer cells that selectively interact with the specific antigen receptor. This ability to target tumors with higher specificity can expedite tumor cell death and eradicate cancer more effectively with longer durations of response.

But there continues to be a learning curve in research of CAR-T therapies. The first generation of CAR-T therapies has been associated with notable toxicities like cytokine release syndrome (CRS), macrophage activation syndrome (MAS), immune effector cell-associated neurotoxicity syndrome (ICANS), and potentially secondary malignancies. Future generation CAR-Ts, however, aim to accelerate therapeutic effect and optimize antigen binding on the tumors, while minimizing toxicities1,2.