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-γ, 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.

中文翻译：

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4-1BB 靶向免疫疗法：机制、抗体和嵌合抗原受体 T。

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来改善癌症免疫治疗。4-1BB与配体结合后，核因子-κB信号通路被激活，导致相应基因（如白介素-2和干扰素-γ）转录，并诱导T细胞增殖和抗凋亡信号。此外，针对4-1BB的单克隆抗体，例如Urelumab和Utomilumab，广泛用于治疗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。此外，4-1BB 作为嵌合抗原受体 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 的更深入了解将有助于癌症免疫治疗的改进。本综述对当前 4-1BB 研究进行了全面分析，重点关注 CAR-T 细胞中靶向 4-1BB 抗体和 4-1BB 激活域用于癌症治疗的用途。