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

ABSTRACT 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.