Department of Medical and Surgical Science, Medical Oncology Unit, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Sarcoma Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Hum Vaccin Immunother. 2023 Dec 31;19(1):2178220. doi: 10.1080/21645515.2023.2178220. Epub 2023 Feb 10.
Immune checkpoint blockers (ICB) act by reverting the immunosuppressive phenotype of cancer cells, thus allowing host immune system to generate an immune response to the tumor. One of the key mechanisms targeted by ICB is the PD-1/PD-L1 axis, which lies onto the interaction between the programmed-cell death protein 1 and its ligand, overexpressed in several tumor types. This interaction leads to the inhibition of T-cell proliferation and their apoptosis and exhaustion. Anti-PD-1/PD-L1 monoclonal antibodies are now the mainstay of treatment for several advanced stage tumors. Dostarlimab is a novel IgG4 anti-PD-1 antibody which has yielded remarkable results in mismatch-repair deficient endometrial cancer and locally advanced rectal cancer. This product review will illustrate the preclinical development of dostarlimab and its pharmacological characteristics, the clinical trials published so far and the ongoing clinical investigations.
免疫检查点抑制剂（ICB）通过逆转癌细胞的免疫抑制表型，从而使宿主免疫系统对肿瘤产生免疫反应。ICB 靶向的关键机制之一是 PD-1/PD-L1 轴，它位于程序性细胞死亡蛋白 1 与其配体之间的相互作用上，在几种肿瘤类型中过表达。这种相互作用导致 T 细胞增殖和凋亡及耗竭的抑制。抗 PD-1/PD-L1 单克隆抗体现在是几种晚期肿瘤的主要治疗方法。Dostarlimab 是一种新型的 IgG4 抗 PD-1 抗体，在错配修复缺陷型子宫内膜癌和局部晚期直肠癌中取得了显著的效果。本产品综述将阐述 dostarlimab 的临床前开发及其药理学特性、迄今为止发表的临床试验和正在进行的临床研究。
