Chimeric antigen receptor (CAR)-redirected T lymphocytes (CAR T cells) show modest therapeutic efficacy in solid tumors. The desmoplastic structure of the tumor and the immunosuppressive tumor microenvironment usually account for the reduced efficacy of CAR T cells in solid tumors. Mild hyperthermia of the tumor reduces its compact structure and interstitial fluid pressure (IFP), increases blood perfusion, releases antigens and promotes the recruitment of endogenous immune cells. Therefore, the combination of mild hyperthermia with the adoptive transfer of CAR T cells could potentially increase the therapeutic index of these cells in solid tumors. We found that the chondroitin sulfate proteoglycan-4 (CSPG4)-specific CAR T cells infused in Nod scid gamma (NSG) mice engrafted with the human melanoma WM115 cell line had superior antitumor activity after photothermal ablation of the tumor. Our findings suggest that photothermal therapy facilitates the accumulation and effector function of CAR T cells within the solid tumor.

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In situ fibrin gel promotes the survival and the biodistribution of CAR-T cells, eliminating residual GBM cells after surgery.

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