异源抗原组装的纳米疫苗增强了 TIL 对肿瘤生长和转移的多功能性。
Heteroantigen-assembled nanovaccine enhances the polyfunctionality of TILs against tumor growth and metastasis.
机构信息
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College; Kunming, Yunnan, 650000, China; State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Hospital, Nanjing Medical University; Nanjing 211166, China; Department of Immunology, Key Laboratory of Immunological Environment and Disease, Key Laboratory of Human Functional Genomics of Jiangsu Province, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Gusu School, Nanjing Medical University; Nanjing 211166, China; Department of Epidemiology, National Vaccine Innovation Platform, Center for Global Health, Nanjing Medical University, Nanjing, China; Department of Central Laboratory, The Affiliated Huai'an N0.1 People's Hospital, Nanjing Medical University, Huai'an, 223300, China.
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College; Kunming, Yunnan, 650000, China.
出版信息
Biomaterials. 2023 Nov;302:122297. doi: 10.1016/j.biomaterials.2023.122297. Epub 2023 Aug 29.
The dysfunction of tumor infiltrating lymphocytes (TILs) directly correlates with out of control of tumor growth and metastasis. New approaches and insightful clarity for rescuing TILs dysfunction are urgently needed. Here, we design two heterogenous antigens based on MHC-I epitope and MHC-II epitope from tumor, and assemble heterogenous antigens by electrostatic interactions and π-π stacking into heteroantigen-assembled nanovaccine (HANV). HANV not only significantly increases the abundance of CD8 and CD4 TILs, but also elicits stronger polyfunctionality of CD8 and CD4 TILs in vivo. Enhanced polyfunctionality of CD8 and CD4 TILs positively correlate to suppression of tumor growth and metastasis in melanoma-bearing mouse models. We also validate that nucleotide-binding oligomerization domain-containing protein 2 (NOD2) dominantly enhances anti-tumor capacity of TILs in a temporal immunoregulation manner. This work presents a new insight in developing HANV as a rational strategy to shape TILs polyfunctionality for tumor growth and metastasis.
肿瘤浸润淋巴细胞（TILs）的功能障碍与肿瘤失控生长和转移直接相关。迫切需要新的方法和有见地的清晰思路来挽救 TILs 的功能障碍。在这里，我们设计了两种基于肿瘤 MHC-I 表位和 MHC-II 表位的异源抗原，并通过静电相互作用和π-π堆积将异源抗原组装成异源抗原组装纳米疫苗（HANV）。HANV 不仅显著增加了 CD8 和 CD4 TILs 的丰度，而且在体内还引发了更强的 CD8 和 CD4 TILs 的多功能性。增强的 CD8 和 CD4 TILs 的多功能性与黑色素瘤荷瘤小鼠模型中肿瘤生长和转移的抑制呈正相关。我们还验证了核苷酸结合寡聚化结构域蛋白 2（NOD2）以时间免疫调节的方式主导增强了 TILs 的抗肿瘤能力。这项工作为开发 HANV 提供了新的见解，将其作为一种合理的策略来塑造 TILs 的多功能性，以抑制肿瘤生长和转移。
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