Yu Liu, Yu Mian, Chen Wei, Sun Shengjie, Huang Wenxin, Wang Tianqi, Peng Zhangwen, Luo Zewen, Fang Yixuan, Li Yongjiang, Deng Yang, Wu Meiying, Tao Wei
School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen 518107, P. R. China.
Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States.
J Am Chem Soc. 2023 Mar 17. doi: 10.1021/jacs.2c12986.
Because of tumor heterogeneity and the immunosuppressive tumor microenvironment, most cancer vaccines typically do not elicit robust antitumor immunological responses in clinical trials. In this paper, we report findings about a bioadhesive nanoparticle (BNP)-based separable cancer vaccine, FeSHK@B-ovalbumin (OVA), to target multi-epitope antigens and exert effective cancer immunotherapy. After the FeSHK@B-OVA "nanorocket" initiates the "satellite-rocket separation" procedure in the acidic tumor microenvironment, the FeSHK@B "launch vehicle" can amplify intracellular oxidative stress persistently. This procedure allows for bioadhesiveness-mediated prolonged drug retention within the tumor tissue and triggers the immunogenic death of tumor cells that transforms the primary tumors into antigen depots, which acts synergistically with the OVA "satellite" to trigger robust antigen-specific antitumor immunity. The cooperation of these two immunostimulants not only efficiently inhibits the primary tumor growth and provokes durable antigen-specific immune activation but also activates a long-term and robust immune memory effect to resist tumor rechallenge and metastasis. These results highlight the enormous potential of FeSHK@B-OVA to serve as an excellent therapeutic and prophylactic cancer nanovaccine. By leveraging the antigen depots and the synergistic effect among multi-epitope antigens, such a nanovaccine strategy with stealthy bioadhesion may offer a straightforward and efficient approach to developing various cancer vaccines for different types of tumors.
由于肿瘤异质性和免疫抑制性肿瘤微环境，大多数癌症疫苗在临床试验中通常无法引发强大的抗肿瘤免疫反应。在本文中，我们报告了一种基于生物粘附纳米颗粒（BNP）的可分离癌症疫苗FeSHK@B-卵清蛋白（OVA）的研究结果，该疫苗可靶向多表位抗原并实施有效的癌症免疫治疗。在酸性肿瘤微环境中，FeSHK@B-OVA“纳米火箭”启动“卫星-火箭分离”程序后，FeSHK@B“运载火箭”可持久放大细胞内氧化应激。这一过程可实现生物粘附介导的肿瘤组织内药物长时间滞留，并触发肿瘤细胞的免疫原性死亡，将原发性肿瘤转化为抗原库，与OVA“卫星”协同作用，触发强大的抗原特异性抗肿瘤免疫。这两种免疫刺激剂的协同作用不仅能有效抑制原发性肿瘤生长并激发持久的抗原特异性免疫激活，还能激活长期且强大的免疫记忆效应，以抵抗肿瘤再次攻击和转移。这些结果凸显了FeSHK@B-OVA作为一种优秀的治疗性和预防性癌症纳米疫苗的巨大潜力。通过利用抗原库以及多表位抗原之间的协同效应，这种具有隐身生物粘附性的纳米疫苗策略可能为开发针对不同类型肿瘤的各种癌症疫苗提供一种直接而有效的方法。
