Therapeutic vaccines offer promising strategies for cancer treatment, however, the lack of key targets among autologous neoantigens and limited variety of synthetic antigens pose significant challenges. Herein, we developed engineered hybrid membrane vesicles (MVs) as a carrier platform, which combines autologous membrane protein antigens derived from resected tumors with synthetic antigens, aiming to inhibit postoperative tumor recurrence. To enhance antitumor immunity, we utilized an optimized AS01 adjuvant, primarily composed of QS-21 and structurally simplified TLR4 agonist GAP-112, to further enhance the immunogenicity of the autologous and synthetic antigens. This extracellular vesicle (EV)-mimicking therapeutic vaccine platform, which includes P (synthetic peptides), M (autologous membrane proteins), G (GAP112), and Q (QS-21), demonstrates potent antitumor effects and effectively suppressed tumor recurrence in three tumor models, including B16-MUC1, EAC, and B16-OVA tumors. Its mechanisms of immune-enhancement include activating innate immunity, enhancing antigen uptake, and inducing robust antibody and cellular immune responses. These results suggest that this engineered hybrid MVs-based carrier platform holds significant potential as a universal strategy for cancer therapy.
