Suzuki Hiroyuki, Ohishi Tomokazu, Nakamura Takuro, Yanaka Miyuki, Handa Saori, Tanaka Tomohiro, Kaneko Mika K, Kato Yukinari
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.
Antibodies (Basel). 2025 Aug 11;14(3):67. doi: 10.3390/antib14030067.
: 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.
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。
