A Cancer-Specific Anti-Podocalyxin Monoclonal Antibody (humPcMab-60) Demonstrated Antitumor Efficacy Against Human Cancer Xenografts

Background: 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 ad-verse effects on normal tissues, the development of a cancer-specific mAb (CasMab) against PODXL is essential. Methods: We established a cancer-specific anti-PODXL mAb, PcMab-60 (IgM, κ), through the screening of over one hundred hybridoma clones. In this study, we engineered PcMab-60 into a humanized IgG1-type mAb (humPcMab-60) and examined its antitumor activity against mouse xenograft models of pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer. Results: HumPcMab-60 retains the can-cer-specific reactivity; humPcMab-60 reacted to PDAC cell lines (MIA PaCa-2 and PK-45H) and 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 PDOXL-expressing cell lines, and showed the antitumor effect against the tumor xenografts. Conclusions: A humanized anti-PODXL CasMab, humPcMab-60, could be a promising mAb-based tumor therapy.