Bibliographic Details
| Title: |
Restoring tumor antigenicity activates the "bystander" T cell immune cycle. |
| Authors: |
Yang, Yifan1 (AUTHOR), Yu, Qiumin1 (AUTHOR), Zhang, Haoyu1 (AUTHOR), Liu, Yuchen1 (AUTHOR), Wang, Hexuan2 (AUTHOR), Yang, Ningyi3 (AUTHOR), Shi, Yulian1 (AUTHOR), Zhang, Wanli1 (AUTHOR), Wu, Zijie1 (AUTHOR), Huang, Shitong1 (AUTHOR), Xie, Wenbin1 (AUTHOR), Duan, Ran1 (AUTHOR), Mao, Qiuli1 (AUTHOR), Shi, Xupeiyao1 (AUTHOR), Gao, Zheng1 (AUTHOR), Wang, Xiaoning1 (AUTHOR), Guo, Hanlin1 (AUTHOR), Chen, Lingxiao1 (AUTHOR), Han, Yi1 (AUTHOR), Li, Ximing1 (AUTHOR) |
| Source: |
Journal of Controlled Release. Apr2025, Vol. 380, p256-268. 13p. |
| Subject Terms: |
*TUMOR antigens, *CELLULAR immunity, *CELL cycle, *TUMOR microenvironment, *PEPTIDES, *T cells |
| Abstract: |
Tumor-specific T cells play a crucial role in tumor immunity. However, these cells are often scarce and functionally exhausted within the tumor microenvironment (TME), leading to the limited efficacy of immunotherapy in many cancer patients. In contrast, increasing evidence suggests that the TME is rich in "bystander" T cells (T BYS), most of which are virus-specific and unrelated to the tumor. These T BYS cells retain functional memory characteristics and the potential to kill tumor cells. To utilize T BYS cells in the TME for tumor elimination, we designed an intracellular delivery system, ASCP, encoding a T BYS epitope to redirect tumor cell antigen specificity toward pre-existing T BYS cells, resulting in effective tumor inhibition in multiple preclinical models. The ASCP-antigen peptide strategy restores the antigenicity of tumor cells and induces epitope spreading of tumor antigens, thereby eliciting more diverse tumor-specific T cell responses. Remarkably, this strategy incorporates MHC-II epitopes containing unnatural amino acids (p -nitrophenylalanine, termed NiraTh), which stimulate CD4+ T cell-mediated immunity and assist CD8+ T cells in clearing tumors. Overall, the ASCP-mediated tumor antigen reprogramming strategy provides important insights for cancer immunotherapy in populations with a history of common viral infections. Reprogramming of tumor antigenicity by ASCP activates "bystander" T-cell immunity. [Display omitted] [ABSTRACT FROM AUTHOR] |
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| Database: |
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