Thermosensitive Nanostructured Hydrogel-Mediated Local Photodynamic Therapy Augments the Antitumor Efficacy of Adoptive T-Cell Therapy

Adoptive transfer of antigen-specific T cells has been shown to be effective in treating hematological malignancies, yet its utility in solid tumor treatment remains constrained, mainly by inadequate tumor antigenicity. To overcome this obstacle, the present study designed an injectable hydrogel encapsulating the photosensitizer Chlorin e6 (Ce6@Gel) for the implementation of photodynamic therapy (PDT). In mice bearing 4T1 tumors, the combined administration of Ce6@Gel-based PDT and adoptive T-cell therapy yielded a marked synergistic antitumor outcome, which was mediated by a 2-fold mechanism. Specifically, PDT not only exerts a direct cytotoxic effect on tumor cells but also induces immunogenic cell death (ICD). The infiltration of both endogenous and adoptively transferred T cells into the tumor site was significantly increased. Collectively, Ce6@Gel promotes the therapeutic efficacy of adoptively transferred T cells in solid tumors, effectively addressing the major challenges currently limiting adoptive T-cell therapy.