Manganese Ions Chelated Tumosomes as Autologous Cancer Nanovaccines for Effective Suppression of Postsurgical Tumor Relapse

Abstract

Autologous cancer vaccines represent a promising strategy to effectively suppress postoperative tumor relapse by eliciting tumor-specific immune responses that highly rely on the efficient internalization and lymph node-targeting delivery of vaccines. Herein, we report an autologous nanovaccine obtained by sequentially incorporating tumor plasma membrane proteins into liposomes, termed tumosomes, and chelating it with metallo-agonist of manganese ions. The yielded Mn-tumosomes with a positively charged surface exhibited significantly enhanced internalization by dendritic cells and enhanced lymph node targeting capacity, the latter of which is indicated by the near-infrared II fluorescence of silver sulfide nanoprobes labeled on their lipid bilayers. As a result, vaccination with Mn-tumosomes elicited potent tumor-specific CD8+ T cells to suppress the growth of challenged allogeneic tumors more effectively than vaccination via bolus injection of plain tumosomes and commercial immune agonists. Furthermore, with the excised tumor mass as the source of whole tumor cell antigens, the as-prepared autologous Mn-tumosomes effectively suppressed the growth of both residual tumor masses and spontaneously formed metastatic tumors, particularly in combination with anti-PD-1 immunotherapy. This work highlights a metal coordination based strategy to fabricate personalized whole-tumor cell nanovaccines with superior lymph node targeting and cellular uptake efficacy for the immunotherapeutic suppression of postoperative tumor relapse.