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                      A tumor-specific pro-IL-12 activates preexisting cytotoxic T cells to control established tumors, Sci Immunol, 7 Jan 2022

                      發布時間:2022年01月07日

                      Science Immunology, 7 January, 2022, DOI:https://doi.org/10.1126/sciimmunol.abi6899

                      A tumor-specific pro-IL-12 activates preexisting cytotoxic T cells to control established tumors

                      Diyuan Xue, Benjamin Moon, Jing Liao, Jingya Guo, Zhuangzhi Zou, Yanfei Han, Shuaishuai Cao, Yang Wang, Yang-Xin Fu and Hua Peng 

                      Abstract

                      It is a challenge to effectively reactivate preexisting tumor-infiltrating lymphocytes (TILs) without causing severe toxicity. Interleukin-12 (IL-12) can potently activate lymphocytes, but its clinical use is limited by its short half-life and dose-related toxicity. In this study, we developed a tumor-conditional IL-12 (pro-IL-12), which masked IL-12 with selective extracellular receptor–binding domains of the IL-12 receptor while preferentially and persistently activating TILs after being unmasked by matrix metalloproteinases expressed by tumors. Systemic delivery of pro-IL-12 demonstrated reduced toxicity but better control of established tumors compared with IL-12-Fc. Mechanistically, antitumor responses induced by pro-IL-12 were dependent on TILs and IFNγ. Furthermore, direct binding of IL-12 to IL-12R on CD8+, not CD4+, T cells was essential for maximal effectiveness. Pro-IL-12 improved the efficacy of both immune checkpoint blockade and targeted therapy when used in combination. Therefore, our study demonstrated that pro-IL-12 could rejuvenate TILs, which then combined with current treatment modalities while limiting adverse effects for treating established tumors.

                      文章鏈接:https://www.science.org/doi/10.1126/sciimmunol.abi6899

                      相關報道:http://www.dengshan5.com/kyjz/zxdt/202201/t20220107_6336897.html

                       

                       

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