A dendritic cell-targeting LNP hybridized with multi-antigen cell membrane for precision cancer immunotherapy

Therapeutic tumor vaccines aim to eradicate tumors by activating the immune system, but the clinical therapeutic effect is usually constrained by insufficient tumor-specific antigen presenting efficiency of dendritic cell (DC) and subsequent T cell identifying. Here, we develop a DC targeting ionizable glycolipid (DOPCO)-based lipid nanoparticles (LNP), which is hybridized with tumor cell membranes and encapsulate TLR7/8 agonist RNAdjuvant, to fabricate cancer cell membrane-derived nanovaccines (CCM/TA-DLNPs) for tumor eradication and prevention. CCM/TA-DLNPs exposing multi-antigens identical to those of the source tumor, can target and deliver personalized antigens to DC facilitated by DOPCO, promoting lymph node accumulation and induction of T-cell immunity. Together with the immunostimulatory adjuvant TA, CCM/TA-DLNPs further amplify systemic immune activation and maintain long-term immunological memory. Impressively, in mice bearing triple-negative breast cancer (TNBC), this personalized strategy systemically evoke specific antitumor immunity and reprogram the immunosuppressive "cold tumor" microenvironment, demonstrating enhanced tumor eradication, reduced recurrence risk, and prolonged survival. This study may contribute to the development of therapeutic and prophylactic vaccines, supporting its further translational testing as an effective individualized anti-tumor immunotherapy.

Abstract from PubMed (PMID 43021546). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.