Dostarlimab

Dostarlimab (TSR-042) is a humanized anti-PD-1 monoclonal antibody. Dostarlimab binds with high affinity to human PD-1 and competitively inhibits its interaction with its ligands, PD-L1 and PD-L2, with IC50s of 1.8 and 1.5 nM, respectively[1].

Research Areas >> Cancer

Signaling Pathways >> Immunology/Inflammation >> PD-1/PD-L1

IC50: 1.5 nM (PD-L2/ PD-1), 1.8 nM (PD-L1/ PD-1)[1]

Dostarlimab (10-10000 ng/mL) 以剂量依赖的方式与人和食蟹猴 CD3+ T 细胞上表达的原生 PD-1 受体结合[1]。 Dostarlimab (0-375 nM; 48 h) 在人 CD4+ T 细胞 MLR 实验中增加 IL-2 的产生，EC50 大约为 1 nM，在葡萄球菌肠毒素 B (SEB) 刺激的 PBMC 细胞中增加 IL-2 的产生，EC50 大约为 0.1 nM，增强干扰素 (IFN)-γ 的释放，EC50 大约为 0.5 nM[1]。

Dostarlimab (200 µg/mouse; i.p.; twice weekly for 35 days) 在人源化小鼠模型中显示出抗肿瘤活性[1]。 Animal Model: Humanized NOG-EXL mice, A549 and MDA-MB-436 tumor model[1] Dosage: 200 µg/mouse Administration: Intraperitoneal injection; twice weekly for 35 days Result: Resulted in great inhibition of tumor growth in an A549 lung cancer model (tumor growth inhibition [TGI] of 62% at termination). The antitumor activity was associated with a reduction in tumor-associated regulatory T cells and a trend toward increased tumor-infiltrating CD8+ T cells. Inhibited tumor growth of MDA-MB-436 breast cancer model (TGI of 53%).

[1]. Kumar S, et al. Preclinical characterization of dostarlimab, a therapeutic anti-PD-1 antibody with potent activity to enhance immune function in in vitro cellular assays and in vivo animal models. MAbs. 2021 Jan-Dec;13(1):1954136.