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普里戈利单抗、帕博利珠单抗和纳武利尤单抗的临床前比较。

Preclinical comparison of prolgolimab, pembrolizumab and nivolumab.

机构信息

JSC BIOCAD, St.-Petersburg, Russia.

Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St.-Petersburg, Russia.

出版信息

Sci Rep. 2024 Oct 4;14(1):23136. doi: 10.1038/s41598-024-72118-3.

Abstract

Prolgolimab is a recombinant IgG1-based anti-PD-1 antibody, whose properties were improved by the introduction of the LALA mutation, and which has demonstrated high efficacy in patients with metastatic melanoma. This paper presents the results of comparative preclinical studies of antigen-binding and effector functions involving prolgolimab and conventional IgG4 antibodies, nivolumab and pembrolizumab. None of the studied antibodies had undesirable antibody-dependent cellular cytotoxicity activity. Prolgolimab has shown higher PD-1 receptor occupancy and T-cell activation, but lower propensity to activate antibody-dependent cellular phagocytosis as compared to nivolumab and pembrolizumab. An in vivo study in mice inoculated with CT26.wt cancer cells showed that tumor growth inhibition was 16% for pembrolizumab and 56% for prolgolimab. This study warrants clinical comparison of IgG1- and IgG4-based anti-PD-1 antibodies.

摘要

普罗利单抗是一种基于 IgG1 的抗 PD-1 抗体,通过引入 LALA 突变改善了其性质,在转移性黑色素瘤患者中显示出了很高的疗效。本文介绍了涉及普罗利单抗和传统 IgG4 抗体(纳武利尤单抗和帕博利珠单抗)的抗原结合和效应功能的比较临床前研究结果。研究中没有一种抗体具有不良的抗体依赖性细胞毒性活性。与纳武利尤单抗和帕博利珠单抗相比,普罗利单抗显示出更高的 PD-1 受体占有率和 T 细胞激活,但对抗体依赖性细胞吞噬作用的激活倾向较低。在接种 CT26.wt 癌细胞的小鼠体内研究中,发现帕博利珠单抗的肿瘤生长抑制率为 16%,而普罗利单抗的肿瘤生长抑制率为 56%。这项研究需要对 IgG1 和 IgG4 基于的抗 PD-1 抗体进行临床比较。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6846/11452378/28e620ab868f/41598_2024_72118_Fig1_HTML.jpg

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