Abstract C127: Chimeric antibody chLpMab-7 targeting human podoplanin suppresses pulmonary metastasis via ADCC and CDC activities

Abstract

Abstract Background: Podoplanin (PDPN), a platelet aggregation-inducing transmembrane glycoprotein, is expressed in a variety of tumors, and binds to C-type lectin-like receptor-2 (CLEC-2). Overexpression of PDPN is involved in invasion and metastasis. Several anti-PDPN monoclonal antibodies (mAbs) such as NZ-1 showed antimetastatic activities by binding to platelet aggregation-stimulating (PLAG) domain of PDPN. Recently, we developed a novel mouse anti-PDPN mAb, LpMab-7 using the cancer-specific mAb (CasMab) method. LpMab-7 is more sensitive than anti-PLAG domain mAbs. Methods: We generated and characterized a mouse-human chimeric anti-PDPN mAb, chLpMab-7. We investigated antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activities in vitro. Furthermore, we evaluated the in vivo efficacy of chLpMab-7 using both xenograft models and experimental metastasis models. In xenograft models, PDPN-expressing CHO (CHO/hPDPN) or a lung cancer cell line PC-10 was engrafted into nude mice. In experimental metastasis models, CHO/hPDPN cells were inoculated into tail vein of the nude mice. Results: ChLpMab-7 antibody showed ADCC and CDC activities against CHO/hPDPN, glioblastoma, mesothelioma, or lung cancer cell lines. Treatment with chLpMab-7 abolished both tumor growth in xenograft and spontaneous pulmonary metastasis. ChLpMab-7 exhibited dramatic suppression of experimental pulmonary metastasis, even when it was injected five days after the inoculation of tumor cells. Conclusion: ChLpMab-7 suppressed tumor development and hematogenous metastasis via ADCC/CDC activities. PDPN should be useful as a novel antibody-based therapy. Citation Format: Yukinari Kato, Mika K. Kaneko. Chimeric antibody chLpMab-7 targeting human podoplanin suppresses pulmonary metastasis via ADCC and CDC activities. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C127.