Uplifting Antitumor Immunotherapy with Lymph-Node-Targeted and Ratio-Controlled Codelivery of Tumor Cell Lysate and Adjuvant.

Abstract

Cancer vaccines provide a potential strategy to cure patients. Their clinical utilization and efficacy is, however, limited by incomplete coverage of tumor neoantigens and unspecific and restricted activation of dendritic cells (DCs). Tumor cell lysates (TCLs) containing a broad spectrum of neoantigens, while are considered ideal in formulating personalized vaccines, induce generally poor antigen presentation and transient antitumor immune response. Here, intelligent polymersomal nanovaccines (PNVs) that quantitatively coload, efficiently codeliver, and responsively corelease TCL and CpG adjuvant to lymph node (LN) DCs are developed to boost antigen presentation and to induce specific and robust antitumor immunity. PNVs carrying CpG and ovalbumin (OVA) markedly enhance the maturation, antigen presentation, and downstream T cell activation ability of bone-marrow-derived dendritic cells and induce strong systemic immune response after tail base injection. Remarkably, PNVs carrying CpG and TCL cure 85% of B16-F10 melanoma-bearing mice and generate long-lasting anticancer immune memory at a low dose, protecting all cured mice from tumor rechallenge. These LN-directed PNVs being highly versatile and straightforward opens a new door for personalized cancer vaccines.