Fusco Riccardo, Saedi Zeinab, Capriello Imma, Lubskyy Andriy, Dömling Alexander
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, and Czech Advanced Technology and Research Institute, Palacky University, Olomouc, Czechia.
Expert Opin Ther Pat. 2025 Jan;35(1):47-64. doi: 10.1080/13543776.2024.2412567. Epub 2024 Nov 25.
The E3 ubiquitin ligase Cbl-b is a novel target in immune-oncology, with critical roles in regulating T-cell activation and signaling pathways. By facilitating the ubiquitination and degradation of key signaling proteins, Cbl-b modulates immune responses, maintaining immune homeostasis and preventing unwarranted T-cell proliferation. The therapeutic potential of Cbl-b as a cancer immunotherapy target is underscored by its contribution to an immunosuppressive tumor microenvironment, with efforts currently underway to develop small-molecule inhibitors.
We reviewed the small molecules, and antibody-drug conjugates targeting Cbl-b from 2018 to 2024. The patents were gathered through publicly available databases and analyzed with in-house developed cheminformatic workflow, described within the manuscript.
Targeting Cbl-b presents a promising approach in immuno-oncology, offering a novel pathway to potentiate the immune system's ability to combat cancer beyond PDL1/PD1 inhibition. The development and clinical advancement of Cbl-b inhibitors, as evidenced by the ongoing trials, mark a significant step toward harnessing this target for therapeutic benefits. Overall, the strategic inhibition of Cbl-b holds substantial promise for improving cancer immunotherapy outcomes, heralding a new era in the fight against cancer.
E3泛素连接酶Cbl-b是免疫肿瘤学中的一个新靶点,在调节T细胞活化和信号通路中起关键作用。通过促进关键信号蛋白的泛素化和降解,Cbl-b调节免疫反应,维持免疫稳态并防止不必要的T细胞增殖。Cbl-b对免疫抑制性肿瘤微环境的作用突出了其作为癌症免疫治疗靶点的治疗潜力,目前正在努力开发小分子抑制剂。
我们回顾了2018年至2024年靶向Cbl-b的小分子和抗体药物偶联物。这些专利通过公开数据库收集,并使用手稿中描述的内部开发的化学信息学工作流程进行分析。
靶向Cbl-b在免疫肿瘤学中是一种有前景的方法,为增强免疫系统对抗癌症的能力提供了一条超越PDL1/PD1抑制的新途径。如正在进行的试验所示,Cbl-b抑制剂的开发和临床进展标志着朝着利用这一靶点获得治疗益处迈出了重要一步。总体而言,对Cbl-b的战略抑制有望显著改善癌症免疫治疗效果,开创抗癌斗争的新时代。