Injectable Porous Microchips with Oxygen Reservoirs and an Immune-Niche Enhance the Efficacy of CAR T Cell Therapy in Solid Tumors.

Chimeric antigen receptor (CAR) T cell therapy is a promising new class of hematological malignancy treatment. However, CAR T cells are rarely effective in solid tumor therapy mainly because of the poor trafficking of injected CAR T cells to the tumor site and their limited infiltration and survival in the immunosuppressive and hypoxic tumor microenvironment (TME). Here, we built an injectable immune-microchip (i-G/MC) system to intratumorally deliver CAR T cells and enhance their therapeutic efficacy in solid tumors. In the i-G/MC, oxygen carriers (Hemo) are released to disrupt the TME, and then, CAR T cells migrate from IL-15-laden i-G/MCs into the tumor stroma. The results indicate that Hemo and IL-15 synergistically enhanced CAR T cell survival and expansion under hypoxic conditions, promoting the potency and memory of CAR T cells. This i-G/MC not only serves as a cell carrier but also builds an immune-niche, enhancing the efficacy of CAR T cells.