Uplifting Anti-tumor Immunotherapy with Lymph Node-targeted and Ratio-controlled Co-delivery of Tumor Cell Lysate and Adjuvant.

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 (TCL) containing a broad spectrum of neoantigens, while are considered ideal in formulating personalized vaccines, induce generally poor antigen presentation and transient anti-tumor immune response. Here, intelligent polymersomal nanovaccines (PNVs) that quantitatively co-load, efficiently co-deliver and responsively co-release TCL and CpG adjuvant to lymph node (LN) DCs are developed to boost antigen presentation and to induce specific and robust anti-tumor immunity. PNVs carrying CpG and OVA (CpG/OVA@PNV) markedly enhanced the maturation, antigen presentation and downstream T cell activation ability of BMDCs and induced strong systemic immune response after tail base injection. Remarkably, PNVs carrying CpG and TCL (CpG/TCL@PNV) cured 85% of B16-F10 melanoma-bearing mice and generated long-lasting anti-cancer immune memory at a low dose, protecting all cured mice from tumor re-challenge. These LN-directed PNVs being highly versatile and straightforward opens a new door for personalized cancer vaccines. This article is protected by copyright. All rights reserved.