Tumor microenvironment-triggered in situ cancer vaccines inducing dual immunogenic cell death for elevated antitumor and antimetastatic therapy

Abstract

Cancer vaccines are made from tumor-specific antigens, which are then injected back into the body to activate immune responses for cancer immunotherapy. Despite the high specificity and therapeutic efficiency, the vaccine has huge challenges such as complex preparation process, expensiveness and limited durational effects. Herein, a strategy to develop in situ cancer vaccines by enhancing the immunomodulatory effects for immunogenic cell death (ICD) is presented. First, amorphous iron oxide-packaged oxaliplatin (AIO_oxp) nanoprodrugs with a high drug loading efficiency of 12.9% were prepared. By utilizing tumor microenvironment (TME) as an endogenous stimulus, this inorganic nanoprodrug can effectively realize TME-responsive combined treatments of chemotherapy and chemodynamic therapy (CDT), and thus achieve dual and precise ICD induction. Further, in vivo immunopotentiation performances further prove that this enhanced ICD effect is able to efficiently promote the maturity of dendritic cells (DCs), T cell activation and correlative cytokine secretion. Furthermore, the obtained nanoprodrugs not only reduce systemic toxicities of Oxp and achieve T₁/T₂ magnetic resonance imaging (MRI), but also dramatically inhibit tumor growth and lung metastasis. We believe that the design of in situ cancer vaccines by enhancing the ICD effects will inspire future studies on cancer vaccines.