肿瘤细胞治疗研究
英文原题：4-1BB Targeting Immunotherapy: Mechanism, Antibodies, and Chimeric Antigen Receptor T.
4-1BB（CD137，TNFRSF9）是一种I型跨膜蛋白，与其天然配体4-1BBL结合。
4-1BB（CD137，TNFRSF9）是一种I型跨膜蛋白，与其天然配体4-1BBL结合。这种相互作用已被用于改进癌症免疫治疗。当4-1BB与配体结合时，核因子-κB信号通路被激活，导致白细胞介素-2和干扰素-等相应基因的转录，以及诱导T细胞增殖和抗凋亡信号。此外，靶向4-1BB的单克隆抗体，例如Urelumab和Utomilumab，广泛用于B细胞非霍奇金淋巴瘤、肺癌、乳腺癌、软组织肉瘤和其他实体瘤的治疗。此外，4-1BB作为CAR-T（CAR-T）细胞的共刺激结构域，可改善T细胞增殖和存活，并减少T细胞耗竭。因此，对4-1BB的更深入理解将有助于改进癌症免疫治疗。本综述对当前4-1BB研究进行了全面分析，重点关注靶向4-1BB抗体和CAR-T细胞中4-1BB激活结构域在癌症治疗中的应用。
4-1BB (CD137, TNFRSF9) is a type I transmembrane protein which binds its natural ligand, 4-1BBL. This interaction has been exploited to improve cancer immunotherapy. With ligand binding by 4-1BB, the nuclear factor-kappa B signaling pathway is activated, which results in transcription of corresponding genes such as interleukin-2 and interferon- , as well as the induction of T cell proliferation and antiapoptotic signals. Moreover, monoclonal antibodies that target-4-1BB, for example, Urelumab and Utomilumab, are widely used in the treatments of B cell non-Hodgkin lymphoma, lung cancer, breast cancer, soft tissue sarcoma, and other solid tumors. Furthermore, 4-1BB as a costimulatory domain, for chimeric antigen receptor T (CAR-T) cells, improves T cell proliferation and survival as well as reduces T cell exhaustion. As such, a deeper understanding of 4-1BB will contribute to improvements in cancer immunotherapy. This review provides a comprehensive analysis of current 4-1BB studies, with a focus on the use of targeting-4-1BB antibodies and 4-1BB activation domains in CAR-T cells for the treatment of cancer.
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