Zheng Jingben, Li Xiaoye, He Ao, Zhang Yu, Yang Yuebo, Dang Meng, Li Qiang, Mou Yongbin, Dong Heng
Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, 30 Zhongyang Road, Nanjing, Jiangsu 210008, China.
National University of Singapore, 21 Lower Kent Ridge Road, 119276, Singapore.
J Control Release. 2025 Sep 10;385:113984. doi: 10.1016/j.jconrel.2025.113984. Epub 2025 Jun 29.
Dendritic cell (DC)-mediated tumor immunotherapy has demonstrated considerable potential, effectively bridging tumor antigens with specific anti-tumor immune responses. However, the heterogeneous and immunosuppressive tumor microenvironment (TME) frequently impairs DC function by inhibiting antigen uptake, restricting differentiation into mature DCs (mDCs), and limiting migration to tumor-draining lymph nodes (TDLNs), ultimately resulting in immune tolerance that diminishes specific anti-tumor immune responses. To overcome these limitations and effectively restore the DC-mediated link between tumor-derived antigens and robust anti-tumor immunity, nanovaccines utilizing in situ antigen-capture strategies have been developed. These strategies uniquely offer personalized and targeted activation of anti-tumor immune responses. In this review, we first address the influence of the TME on DC functionality, highlighting the numerous immunosuppressive factors that restrict efficient antigen uptake by DCs. Subsequently, we detail the core mechanisms underlying in situ antigen-capturing nanovaccines (AC-NVs), including covalent, noncovalent, and combined antigen capture methods. Furthermore, recent advances in AC-NVs constructed from various biomaterials are reviewed, emphasizing their intrinsic material properties and antigen-capturing capabilities for functionalizing DCs and enhancing specific anti-tumor immunity. Finally, we discuss current challenges and future perspectives for AC-NVs, emphasizing their potential role in developing personalized cancer vaccines, optimizing immune responses, and facilitating clinical translation.
树突状细胞（DC）介导的肿瘤免疫疗法已显示出巨大潜力，能有效地将肿瘤抗原与特异性抗肿瘤免疫反应联系起来。然而，异质性和免疫抑制性的肿瘤微环境（TME）常常通过抑制抗原摄取、限制分化为成熟树突状细胞（mDC）以及限制向肿瘤引流淋巴结（TDLN）迁移来损害DC功能，最终导致免疫耐受，削弱特异性抗肿瘤免疫反应。为克服这些限制并有效恢复DC介导的肿瘤衍生抗原与强大抗肿瘤免疫之间的联系，已开发出利用原位抗原捕获策略的纳米疫苗。这些策略独特地提供了个性化和靶向性的抗肿瘤免疫反应激活。在本综述中，我们首先探讨TME对DC功能的影响，强调众多限制DC有效摄取抗原的免疫抑制因子。随后，我们详细阐述原位抗原捕获纳米疫苗（AC-NV）的核心机制，包括共价、非共价和联合抗原捕获方法。此外，还综述了由各种生物材料构建的AC-NV的最新进展，强调其内在材料特性和用于DC功能化及增强特异性抗肿瘤免疫的抗原捕获能力。最后，我们讨论了AC-NV目前面临的挑战和未来前景，强调其在开发个性化癌症疫苗、优化免疫反应及促进临床转化中的潜在作用。
