Pembrolizumab, an anti–programmed death-1 monoclonal antibody, has demonstrated clinically significant anti-tumor activity with acceptable safety in patients with advanced solid cancers and was approved by the U.S. FDA for the treatment of advanced melanoma, NSCLC, head and neck squamous cell cancer, and other malignant tumors.[1]
In vitro study demonstrated that pembrolizumab had a greater effect on PD-1 expression in CD4+CD25- T cells which expressed most of the PD-1, and that are comprised of non-Treg and/or non-activated T cells. However, pembrolizumab did not affect the expression levels of Treg-related markers, including cytotoxic T lymphocyte antigen-4 (CTLA-4), CD15s, latency-associated peptide (LAP) and Ki-67 as well as the levels of FoxP3+/-Helios+/- Treg subsets in both cohorts.[2]
In vivo study of pembrolizumab indicated that in Onco-Humanized NSG mice, pembrolizumab could inhibit tumor growth, not only in CDX but also in various PDX tumor models. Results showed that the efficacy of pembrolizumab is dependent on the engraftment of an adaptive human immune system in Onco-Humanized NSG mice, specifically hCD8+ T cells. Furthermore, pembrolizumab increased both CD4+ and CD8+ T-cell numbers in the blood of the 2 NSCLC Onco-Humanized NSG models but decreased both CD4+ and CD8+ T-cell numbers in the blood of the TNBC Onco-Humanized NSG model.[3]
References:
[1]. Mo DC, et al. Safety and efficacy of pembrolizumab plus lenvatinib versus pembrolizumab and lenvatinib monotherapies in cancers: A systematic review. Int Immunopharmacol. 2021 Feb;91:107281.
[2]. Toor SM, et al. In-vitro effect of pembrolizumab on different T regulatory cell subsets. Clin Exp Immunol. 2018 Feb;191(2):189-197.
[3]. Wang M, et al. Humanized mice in studying efficacy and mechanisms of PD-1-targeted cancer immunotherapy. FASEB J. 2018 Mar;32(3):1537-1549.
Pembrolizumab 是一种抗程序性死亡 1 单克隆抗体，已在晚期实体癌患者中证明具有临床显着的抗肿瘤活性和可接受的安全性，并已被美国 FDA 批准用于治疗晚期黑色素瘤、NSCLC、头颅和脑肿瘤。颈部鳞状细胞癌等恶性肿瘤。[1]
体外研究表明，派姆单抗对 CD4+CD25-T 细胞中的 PD-1 表达有更大的影响，这些细胞表达大部分 PD-1，并且由非 Treg 和/或未激活的 T 细胞组成。然而，pembrolizumab 不影响 Treg 相关标志物的表达水平，包括细胞毒性 T 淋巴细胞抗原 4 (CTLA-4)、CD15s、潜伏相关肽 (LAP) 和 Ki-67 以及 FoxP3+/- Helios+/- 两个队列中的 Treg 子集。[2]
pembrolizumab 的体内研究表明，在 Onco-Humanized NSG 小鼠中，pembrolizumab 可以抑制肿瘤生长，不仅在 CDX 中，而且在各种 PDX 肿瘤模型中。结果表明，pembrolizumab 的疗效取决于适应性人类免疫系统在 Onco-Humanized NSG 小鼠中的植入，特别是 hCD8+ T 细胞。此外，pembrolizumab 增加了 2 个 NSCLC Onco-Humanized NSG 模型血液中的 CD4+ 和 CD8+ T 细胞数量，但减少了 TNBC Onco-Humanized NSG 模型血液中的 CD4+ 和 CD8+ T 细胞数量。[ 3]