Remodeling of Tumor Microenvironment by Tumor‐Targeting Nanozymes Enhances Immune Activation of CAR T Cells for Combination Therapy

Targeting B7‐H3 chimeric antigen receptor (CAR) T cells has antitumor potential for therapy of non‐small cell lung cancer (NSCLC) in preclinical studies. However, CAR T cell therapy remains a formidable challenge for the treatment of solid tumors due to the heterogeneous and immunosuppressive tumor microenvironment (TME). Nanozymes exhibit merits modulating the immunosuppression of the tumor milieu. Here, a synergetic strategy by combination of nanozymes and CAR T cells in solid tumors is described. This nanozyme with dual photothermal‐nanocatalytic properties is endowed to remodel TME by destroying its compact structure. It is found that the B7‐H3 CAR T cells infused in mice engrafted with the NSCLC cells have superior antitumor activity after nanozyme ablation of the tumor. Importantly, it is found that the changes altered immune‐hostile cancer environment, resulting in enhanced activation and infiltration of B7‐H3 CAR T cells. The first evidence that the process of combination nanozyme therapy effectively improves the therapeutic index of CAR T cells is presented. Thus, this study clearly supports that the TME‐immunomodulated nanozyme is a promising tool to improve the therapeutic obstacles of CAR T cells against solid tumors. Nanozyme‐mediated photothermal‐nanocatalytic (PNC) effect enhances the immune response of chimeric antigen receptor (CAR) T cells against solid tumors. The PNC effect disrupts the tumor extracellular matrix and enables tumor cells to be susceptible to CAR T cells. The alterations in the tumor microenvironment ultimately promote tumor infiltration and activation of CAR T cells.