一种抗血小板内皮细胞黏附分子的人源化去岩藻糖基化抗体（humLpMab-23-f）在人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.

作者信息

Suzuki Hiroyuki, Ohishi Tomokazu, Kaneko Mika K, Kato Yukinari

机构信息

Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan.

Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan.

出版信息

Cancers (Basel). 2023 Oct 20;15(20):5080. doi: 10.3390/cancers15205080.

A cancer-specific anti-PDPN mAb, LpMab-23 (mouse IgG, kappa), was established in our previous study. We herein produced a humanized IgG version (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.

在我们之前的研究中建立了一种癌症特异性抗PDPN单克隆抗体LpMab - 23（小鼠IgG，κ链）。我们在此制备了抗PDPN单克隆抗体的人源化IgG版本（humLpMab - 23）和去岩藻糖基化形式（humLpMab - 23 - f），以增强抗体依赖的细胞介导的细胞毒性（ADCC）活性。通过流式细胞术，humLpMab - 23识别过表达PDPN的中国仓鼠卵巢（CHO）- K1（CHO/PDPN）细胞、PDPN阳性的PC - 10（人肺鳞状细胞癌）细胞和LN319（人胶质母细胞瘤）细胞。然后我们证明，humLpMab - 23 - f在体外可诱导针对CHO/PDPN、PC - 10和LN319细胞的ADCC和补体依赖性细胞毒性，并在小鼠异种移植模型中发挥高抗肿瘤活性，这表明humLpMab - 23 - f可作为针对PDPN阳性肺鳞状细胞癌和胶质母细胞瘤的抗体疗法。