Antigen Spreading via Localized Administration Enhances Adoptive TCR-T Cell Therapy in Pancreatic Cancer.

Cancer vaccines have demonstrated initial effectiveness in the treatment of human cancers, still the low mutational burden, which leads to a deficiency of well-characterized antigens expressed within tumors capable of mediating tumor rejection, poses a significant challenge in pancreatic cancer. Here, we introduce an ionic liquid ILvax for localized tumor administration, which elicits a systemic and antigen-specific anti-tumor immune response, thereby generating a vaccine-like effect. Type 1 conventional dendritic cells (cDC1) is the determinant for systemic immune response. ILvax ablation facilitates migration of tumor antigen-carrying cDC1 to peripheral lymphoid organs, thus initiating the cDC1-mediated antigen presentation cascade that results in an amplified antigen-specific T cells response. Meanwhile, cDC1-mediated antigen spreading induced by ILvax enabled the expansion of adoptive TCR-T while shifting TCR-T metabolism toward oxidative phosphorylation (OXPHOS). Localized tumor administration with ILvax simultaneously enhances the functionality of both endogenous CD8+ T cells and adoptive TCR-T cells, offering a clinically translatable collaborative strategy against pancreatic cancer.