The SpyCatcher-SpyTag interaction mediates tunable anti-tumor cytotoxicity of NK cells.
The SpyCatcher-SpyTag interaction mediates tunable anti-tumor cytotoxicity of NK cells.
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DOI：
10.1016/j.molimm.2023.12.001
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发表时间：
2023-12
影响因子：
3.6
通讯作者：
Changjiang Guo;Xiali Guo;Xiaojuan Li;Meng Dong;Xiang Wang;Shizhuang Cheng;Lingtong Zhi;Zhiyuan Niu;Wuling Zhu
中科院分区：
文献类型：
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作者：
Changjiang Guo;Xiali Guo;Xiaojuan Li;Meng Dong;Xiang Wang;Shizhuang Cheng;Lingtong Zhi;Zhiyuan Niu;Wuling Zhu
嵌合抗原受体修饰的T和NK细胞免疫疗法是一种很有前途的癌症治疗方法。由于抗肿瘤活性缺乏可调性，传统的CAR疗法在低肿瘤抗原密度下疗效有限。为了调整CAR对肿瘤细胞表面抗原的反应，我们开发了一种使用SpyCatcher-SpyTag系统的分裂CAR。SpyCatcher作为外域构成SpyCatcher- car (SpyCAR)，而SpyTag则附着在识别肿瘤抗原的抗体上。在SpyCatcher和SpyTag介导的二聚化过程中，被肿瘤抗原募集的SpyCARs的数量和激活水平取决于“抗体-SpyTag”融合蛋白中SpyTag的数量。结果表明，增加SpyTags数量可以有效增强SpyCAR-NK92细胞对靶细胞的细胞毒性。具有可调细胞毒性的SpyCAR的开发为基于car的肿瘤免疫治疗提供了一种新的策略。
Chimeric antigen receptor (CAR)-modified T and NK cell immunotherapy is a promising approach for cancer treatment. Due to the lack of tunability in anti-tumor activity, conventional CAR therapies have limited efficacy at low tumor antigen densities. To tune the CAR response to tumor cell surface antigens, we have developed a split CAR using the SpyCatcher-SpyTag system. The SpyCatcher serves as the ectodomain to constitute a SpyCatcher-CAR (SpyCAR), while SpyTag is attached to the antibodies that recognize tumor antigens. With dimerization mediated by SpyCatcher and SpyTag, the number and activation level of SpyCARs recruited by tumor antigens depends on the SpyTag number in the “antibody-SpyTag” fusion protein. The results demonstrated that the increasing number of SpyTags effectively enhanced the cytotoxicity of SpyCAR-NK92 cells against target cells. The development of SpyCAR with tunable cytotoxicity provides a novel strategy for CAR-based tumor immunotherapies.