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 <i>via</i> 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.