Developing a Personalized Cancer Nanovaccine Using Coxsackievirus-Reprogrammed Cancer Cell Membranes for Enhanced Anti-Tumor Immunity.

Cancer vaccines emerge as a promising approach in immunotherapy, but their efficacy is often hindered by immunosuppressive factors like PD-L1 on tumor cell membranes. To address this challenge, a personalized nanovaccine is developed using membranes from Coxsackievirus B3 (CVB3)-infected 4T1 breast cancer cells combined with heat-deactivated CVB3 (hdCVB3) encapsulated in PLGA nanoparticles (PLGA@hdCVB3I4T1M). RNA sequencing reveals significant upregulation of immune activation-related genes, while protein analysis demonstrates reduced immunosuppressive markers (PD-L1, B7-H3, CD47) and increased immunostimulatory proteins (calreticulin), enhancing immune cell uptake and activation. In vitro and in vivo studies confirm the safety and potent immunostimulatory effects of PLGA@hdCVB3I4T1M, leading to enhanced immune cell infiltration, elevated proinflammatory cytokine production, and robust antitumor responses. The nanovaccine significantly improves tumor suppression and prolongs survival in animal models. Additionally, the inclusion of hdCVB3 amplified immune recognition of both viral and tumor antigens, further enhancing therapeutic efficacy, particularly when combined with oncolytic virotherapy. Mechanistically, this strategy primes the immune system for a more effective and sustained antitumor response. In summary, PLGA@hdCVB3I4T1M effectively stimulates the immune system, overcoming tumor immune evasion. This nanovaccine represents a promising strategy for enhancing cancer immunotherapy and holds strong potential for clinical translation, particularly in combination with oncolytic virotherapy.