Chimeric antigen receptor (CAR) T-cells have become a standard therapy for many hematologic malignancies. While many CAR T-cells are being produced commercially and are in clinical trials, more CAR T-cells are being developed, particularly for the treatment of patients with solid tumors. Unlike most other therapies used to treat cancer and hematologic malignancies, CAR T-cells are biological agents which are most often produced from a patient’s own T-cells. A critical part of the development of new CAR T-cells is identifying the characteristics that are responsible for their potency, toxicity, and clinical effectiveness which often vary among patients. We describe factors responsible for CAR T-cell potency, ongoing work focused on understanding critical characteristics of CAR T-cells contributing to their potency and safety, and ways to improve their potency. Since the factors affecting CAR T-cell potency are dependent on their structure and manufacturing methods, the nature of CAR vectors and CAR T-cell manufacturing methods are also reviewed. When assessing CAR T-cell potency in vitro studies provide valuable information, but it is also important to use data obtained from early clinical trials of specific CAR T-cells to advance the understanding of factors and characteristics that contribute to CAR T-cell potency, safety and clinical effectiveness.
Stroncek et al. (Tue,) studied this question.