一种癌症特异性抗足突细胞粘附分子单克隆抗体（humPcMab-60）在胰腺癌和结直肠癌异种移植模型中显示出抗肿瘤疗效。

A Cancer-Specific Anti-Podocalyxin Monoclonal Antibody (humPcMab-60) Demonstrated Antitumor Efficacy in Pancreatic and Colorectal Cancer Xenograft Models.

作者信息

Suzuki Hiroyuki, Ohishi Tomokazu, Nakamura Takuro, Yanaka Miyuki, Handa Saori, Tanaka Tomohiro, Kaneko Mika K, Kato Yukinari

机构信息

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

Institute of Microbial Chemistry (BIKAKEN), Laboratory of Oncology, Microbial Chemistry Research Foundation, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.

出版信息

Antibodies (Basel). 2025 Aug 11;14(3):67. doi: 10.3390/antib14030067.

DOI:10.3390/antib14030067

PMID:40843679

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12372045/

Abstract

: Podocalyxin (PODXL) has been identified as a promising therapeutic target and a potential diagnostic biomarker in various tumors. Despite the therapeutic potential of anti-PODXL monoclonal antibodies (mAbs), their further development has been limited by concerns regarding potential on-target off-tumor toxicities. To minimize adverse effects on normal tissues, developing a cancer-specific mAb (CasMab) against PODXL is essential. : Our group established a cancer-specific anti-PODXL mAb, PcMab-60 (IgM, κ), through the screening of over one hundred hybridoma clones. In this study, PcMab-60 was engineered into a humanized IgG-type mAb (humPcMab-60), and its antitumor activity was examined using mouse xenograft models of pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer. : HumPcMab-60 retains cancer-specific reactivity; humPcMab-60 reacted to PDAC cell lines (PK-45H and MIA PaCa-2) and the colorectal cancer cell line (Caco-2), but not to a normal lymphatic endothelial cell line in flow cytometry. Furthermore, humPcMab-60 exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against PODXL-expressing cell lines and showed antitumor effects against the tumor xenografts. : A humanized anti-PODXL CasMab, humPcMab-60, could be a promising mAb-based tumor therapy.

摘要

足细胞毒素（PODXL）已被确定为多种肿瘤中有前景的治疗靶点和潜在的诊断生物标志物。尽管抗PODXL单克隆抗体（mAb）具有治疗潜力，但其进一步开发受到对潜在的靶上脱肿瘤毒性担忧的限制。为了使对正常组织的不良影响最小化，开发针对PODXL的癌症特异性mAb（CasMab）至关重要。

我们团队通过筛选一百多个杂交瘤克隆，建立了一种癌症特异性抗PODXL mAb，即PcMab - 60（IgM，κ）。在本研究中，将PcMab - 60改造为人源化IgG型mAb（humPcMab - 60），并使用胰腺导管腺癌（PDAC）和结直肠癌的小鼠异种移植模型检测其抗肿瘤活性。

HumPcMab - 60保留了癌症特异性反应性；在流式细胞术中，humPcMab - 60与PDAC细胞系（PK - 45H和MIA PaCa - 2）以及结直肠癌细胞系（Caco - 2）反应，但不与正常淋巴管内皮细胞系反应。此外，humPcMab - 60对表达PODXL的细胞系发挥抗体依赖性细胞毒性和补体依赖性细胞毒性，并对肿瘤异种移植显示出抗肿瘤作用。

一种人源化抗PODXL CasMab，humPcMab - 60，可能是一种有前景的基于mAb的肿瘤治疗药物。