Leveraging Senescent Cancer Cell Membrane to Potentiate Cancer Immunotherapy Through Biomimetic Nanovaccine

Abstract Senescent cancer cells are endowed with high immunogenic potential that has been leveraged to elicit antitumor immunity and potentially complement anticancer therapies. However, the efficacy of live senescent cancer cell‐based vaccination is limited by interference from immunosuppressive senescence‐associated secretory phenotype and pro‐tumorigenic capacity of senescent cells. Here, a senescent cancer cell‐based nanovaccine with strong immunogenicity and favorable potential for immunotherapy is reported. The biomimetic nanovaccine integrating a senescent cancer cell membrane‐coated nanoadjuvant outperforms living senescent cancer cells in enhancing dendritic cells (DCs) internalization, improving lymph node targeting, and enhancing immune responses. In contrast to nanovaccines generated from immunogenic cell death‐induced tumor cells, senescent nanovaccines facilitate DC maturation, eliciting superior antitumor protection and improving therapeutic outcomes in melanoma‐challenged mice with fewer side effects when combined with αPD‐1. The study suggests a versatile biomanufacturing approach to maximize immunogenic potential and minimize adverse effects of senescent cancer cell‐based vaccination and advances the design of biomimetic nanovaccines for cancer immunotherapy.