CAR-T cells with co-expressed cytokines and chemokines better overcome inhibitory microenvironment of solid tumors

Abstract

The Letter report to Nature Biotechnology by Keishi Adachi, et al. March 5, 2018 describes an elegant approach to combine CD20-CAR-T cells that co-express IL-7 and CCL19, called (7 × 19 CAR-T cells) [4] (Figure 1). Both IL-7 and CCL19 are critical factors to support survival of T cells in lymph nodes and lymphoid tissues. In solid tumor xenograft mice mode, these CD20 CAR-T cells had 100% survival compared with lower survival of standard or conventional CAR-T cells. The anti-tumor effect of 7x19 CAR-T cells was the same when CD28 or 41-BB co-stimulatory domains were designed inside CAR construct [1]. In addition, these CAR-T cells expressed significantly lower levels of LAG-3, TIM-3, PD-1 and other checkpoint inhibitors compared with standard CAR-T cells which demonstrates their less exhausted phenotype. In addition, 7x19 CAR-T cells had increased migratory and increased memory functions that are key functions for increased efficacy of CAR-T cells.