Shi-Hao Zhou , Yu-Juan Lei , Yu Wen , Dong Ding , Meng-Qiang Luo , Hong-Ying Cui , Jun Guo
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Engineered hybrid membrane vesicles combined with autologous and synthetic antigens as therapeutic vaccines to efficiently suppress tumor recurrence
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.
期刊介绍:
The Journal of Controlled Release (JCR) proudly serves as the Official Journal of the Controlled Release Society and the Japan Society of Drug Delivery System.
Dedicated to the broad field of delivery science and technology, JCR publishes high-quality research articles covering drug delivery systems and all facets of formulations. This includes the physicochemical and biological properties of drugs, design and characterization of dosage forms, release mechanisms, in vivo testing, and formulation research and development across pharmaceutical, diagnostic, agricultural, environmental, cosmetic, and food industries.
Priority is given to manuscripts that contribute to the fundamental understanding of principles or demonstrate the advantages of novel technologies in terms of safety and efficacy over current clinical standards. JCR strives to be a leading platform for advancements in delivery science and technology.