CAR 高表达强度赋予增强的抗淋巴瘤作用且不伴功能性耗竭

Identifying factors that ameliorates clinical outcomes following CART therapy represents an unmet need.

We hypothesized that CAR expression level would have a significant impact on CART efficacy and tested this with CAR30 + T SCM - LIKE enriched cells. By sorting T-cells according to CAR mean fluorescence intensity in two markedly different populations (CAR HI and CAR LO ), we showed that a high CAR expression enhances antitumor efficacy in vitro, that is sustained after sequential re-exposures to tumor cells and is not associated with T-cell exhaustion or differentiation.

Furthermore, we found a correlation between high surface CAR expression and antitumor effect with CAR19 + T-cells, thus validating our findings with CAR30. Definitive proof of CAR HI T-cells improved antitumor efficacy was demonstrated in a human Hodgkin's lymphoma xenograft mouse model, where CAR30-T SCM - LIKE enriched products with high intensity of CAR expression achieved superior tumor control in vivo and longer survival than those with a low intensity of CAR expression.

Our data suggest that modulation of CAR intensity of expression represents an additional strategy to increase CART therapy clinical efficacy.