Anti‐Tumor Immunity Induced by a Ternary Membrane System Derived From Cancer Cells, Dendritic Cells, and Bacteria

Abstract Cancer vaccines generally are limited by insufficient tumor‐specific cellular immunogenicity. Herein, a potent “ABC” ternary membrane‐derived vaccine system blended from antigen‐presenting mature dendritic cell membranes (“A”), bacterial E. coli cytoplasmic membranes (“B”), and cancer cell membranes (“C”) is developed using a block‐copolymer micelle‐enabled approach. The respective ABC membrane components provide for a source of cellular immune communication/activation and enhanced accumulation in lymph nodes (A), immunological adjuvant (B), and tumor antigens (C). The introduction of dendritic cell (DC) membranes enables multiple cell‐to‐cell communication and powerful immune activation. ABC activates dendritic cells and promotes T‐cell activation and proliferation in vitro. In vivo, ABC is 14‐ and 304‐fold more immunogenic than binary (BC) and single (C) membrane vaccines, and immunization with ABC enhances the frequency of tumor‐specific cytotoxic T lymphocytes, leading to an 80% cure rate in tumor‐bearing mice. In a surgical resection and recurrence model, ABC prevents recurrence with vaccination from autologous cancer membranes, and therapeutic effects are observed in a lung metastasis model even with heterologous cancer cell membranes. ABCs formed from human cancer patient‐derived tumor cells activate human monocyte‐derived dendritic cells (moDC). Taken together, the ternary ABC membrane system provides the needed functional components for personalized cancer immunotherapy.