文章：

抗Podoplanin人源化及去岩藻糖基化抗体（humLpMab-23-f）在人类肺癌和胶质母细胞瘤异种移植模型中发挥抗肿瘤活性

A Humanized and Defucosylated Antibody against Podoplanin (humLpMab-23-f) Exerts Antitumor Activities in Human Lung Cancer and Glioblastoma Xenograft Models

原文发布日期：20 October 2023

DOI: 10.3390/cancers15205080

类型: Article

开放获取: 是

英文摘要：

A cancer-specific anti-PDPN mAb, LpMab-23 (mouse IgG1, kappa), was established in our previous study. We herein produced a humanized IgG1version (humLpMab-23) and defucosylated form (humLpMab-23-f) of an anti-PDPN mAb to increase ADCC activity. humLpMab-23 recognized PDPN-overexpressed Chinese hamster ovary (CHO)-K1 (CHO/PDPN), PDPN-positive PC-10 (human lung squamous cell carcinoma), and LN319 (human glioblastoma) cells via flow cytometry. We then demonstrated that humLpMab-23-f induced ADCC and complement-dependent cytotoxicity against CHO/PDPN, PC-10, and LN319 cells in vitro and exerted high antitumor activity in mouse xenograft models, indicating that humLpMab-23-f could be useful as an antibody therapy against PDPN-positive lung squamous cell carcinomas and glioblastomas.

摘要翻译： 

在我们先前的研究中，已成功建立了一种癌症特异性抗PDPN单克隆抗体LpMab-23（鼠源IgG1，κ型）。本研究通过制备该抗体的人源化IgG1版本（humLpMab-23）及其去岩藻糖化变体（humLpMab-23-f），以增强其抗体依赖性细胞介导的细胞毒作用活性。流式细胞术检测显示，humLpMab-23能特异性识别过表达PDPN的中国仓鼠卵巢细胞（CHO/PDPN）、PDPN阳性的人肺鳞癌细胞PC-10以及人胶质母细胞瘤细胞LN319。进一步研究表明，humLpMab-23-f在体外能有效诱导针对CHO/PDPN、PC-10和LN319细胞的抗体依赖性细胞介导的细胞毒作用及补体依赖性细胞毒作用，并在小鼠异种移植模型中展现出显著的抗肿瘤活性。这些结果表明，humLpMab-23-f有望成为治疗PDPN阳性肺鳞状细胞癌和胶质母细胞瘤的有效抗体疗法。

原文链接：

A Humanized and Defucosylated Antibody against Podoplanin (humLpMab-23-f) Exerts Antitumor Activities in Human Lung Cancer and Glioblastoma Xenograft Models