Neoantigen enriched biomimetic nanovaccine for personalized cancer immunotherapy

Abstract

Abstract Personalized cancer vaccines elicit robust T cell immunity and anti-tumour potency, but identifying tumour-specific antigens remains challenging, severely constraining the therapeutic window. Biomimetic nanovaccines employing cancer cell membranes display inherent biocompatibility and stimulate T-cell responses against diverse tumour antigens, though tumours develop multiple mechanisms to reduce antigen presentation. Here we demonstrate a rapid and general strategy to fabricate personalized nanovaccines based on Antigen-Enriched tumor Cell Membranes (AECM) for early intervention. Interferon-γ potently stimulates antigen presentation across a broad range of cancer cell types. By coupling the generated AECM with PC7A adjuvant, a stimulator of interferon genes (STING)-activating polymer, the AECM@PC7A nanovaccine induces robust poly-neoepitopic T-cell responses even at low dosage, achieving significant tumour regression and metastasis inhibition in multiple murine cancer models. This anti-tumor response relies on MHC-I restricted antigen presentation and CD8+ T-cell activation, with dendritic cells presenting AECM antigens predominantly via cross-dressing to prime T-cells. AECM@PC7A exhibits remarkable anti-tumor efficacy when compared to vaccines with diverse formulations, and demonstrates therapeutic potential in post-surgical and humanized xenograft tumor models. This proof-of-concept study provides a promising universal avenue for the rapid development of personalized cancer vaccines applicable to early intervention for a broad range of patients.