免疫疗法
白喉毒素
抗原
肿瘤微环境
癌症研究
免疫系统
癌症免疫疗法
肿瘤抗原
免疫学
T细胞
生物
毒素
生物化学
作者
Muye He,Yuji Sun,Yi An Cheng,Jie Wang,Miao Zhang,Rui Sun,Xinyu Hou,Jiajun Xu,Hai He,Qingyuan Wang,Zeting Yuan,Minbo Lan,Yuzheng Zhao,Yi Yang,Xianjun Chen,Feng Gao
标识
DOI:10.1016/j.jconrel.2022.08.059
摘要
Individualized immunotherapy has attracted great attention due to its high specificity, effectiveness, and safety. We used an exogenous antigen to label tumor cells with MHC I molecules, which allowed neoantigen-specific T cells to recognize and kill tumor cells. A neoantigen vaccine alone cannot achieve complete tumor clearance due to a tumor immunosuppressive microenvironment. The LightOn system was developed to effectively eliminate tumor cells through the spatiotemporally controllable expression of diphtheria toxin A fragment, leading to antigen release in the tumor region. These antigens stimulated and enhanced immunological function and thus, recruited neoantigen-specific T cells to infiltrate tumor tissue. Using the nanoparticle delivery system, neoantigens produced higher delivery efficiency to lymph nodes and improved tumor targeting ability for tumor cell labelling. Good tumor inhibition and prolonged survival were achieved, while eliciting a strong immune response. The combination of a spatiotemporally controllable transgene system with tumor neoantigen labeling has great potential for tumor immunotherapy.
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