Cancer Cell Membrane-Coated Adjuvant Nanoparticles with Mannose Modification for Effective Anticancer Vaccination

TLDR

Tumor vaccines have attracted significant interest in cancer immunotherapy. The study proposes a strategy to build cancer vaccines by encapsulating immune‑adjuvant nanoparticles with mannose‑modified cancer cell membranes. The authors loaded PLGA nanoparticles with the TLR7 agonist imiquimod, coated them with cancer‑cell membranes to present tumor antigens, and further added mannose to boost dendritic‑cell uptake. The mannose‑modified nanovaccine induced strong dendritic‑cell activation, delayed tumor growth as a preventive vaccine, and, when combined with checkpoint blockade, achieved superior therapeutic efficacy against established tumors, suggesting broad applicability.

Abstract

Tumor vaccines for cancer prevention and treatment have attracted tremendous interests in the area of cancer immunotherapy in recent years. In this work, we present a strategy to construct cancer vaccines by encapsulating immune-adjuvant nanoparticles with cancer cell membranes modified by mannose. Poly(d,l-lactide-co-glycolide) nanoparticles are first loaded with toll-like receptor 7 agonist, imiquimod (R837). Those adjuvant nanoparticles (NP-R) are then coated with cancer cell membranes (NP-R@M), whose surface proteins could act as tumor-specific antigens. With further modification with mannose moiety (NP-R@M-M), the obtained nanovaccine shows enhanced uptake by antigen presenting cells such as dendritic cells, which would then be stimulated to the maturation status to trigger antitumor immune responses. With great efficacy to delay tumor development as a prevention vaccine, vaccination with such NP-R@M-M in combination with checkpoint-blockade therapy further demonstrates outstanding therapeutic efficacy to treat established tumors. Therefore, our work presents an innovative way to fabricate cancer nanovaccines, which in principle may be applied for a wide range of tumor types.