Preprint Article Version 1 This version is not peer-reviewed

A Cancer-Specific Anti-Podoplanin Monoclonal Antibody, PMab-117-mG2a Exerted Antitumor Activities in Human Tumor Xenograft Models

Version 1 : Received: 6 October 2024 / Approved: 7 October 2024 / Online: 7 October 2024 (13:42:50 CEST)

How to cite: Tanaka, T.; Suzuki, H.; Ohishi, T.; Kaneko, M. K.; Kato, Y. A Cancer-Specific Anti-Podoplanin Monoclonal Antibody, PMab-117-mG2a Exerted Antitumor Activities in Human Tumor Xenograft Models. Preprints 2024, 2024100464. https://doi.org/10.20944/preprints202410.0464.v1 Tanaka, T.; Suzuki, H.; Ohishi, T.; Kaneko, M. K.; Kato, Y. A Cancer-Specific Anti-Podoplanin Monoclonal Antibody, PMab-117-mG2a Exerted Antitumor Activities in Human Tumor Xenograft Models. Preprints 2024, 2024100464. https://doi.org/10.20944/preprints202410.0464.v1

Abstract

Podoplanin (PDPN) overexpression is associated with poor clinical outcomes in various tumors. PDPN is involved in tumor malignant progression by promoting invasiveness and metastasis. Therefore, PDPN is considered a promising target of monoclonal antibody (mAb)-based therapy. Because PDPN also plays an essential role in normal cells such as kidney podocytes, cancer specificity is required to reduce adverse effects on normal cells. We developed cancer-specific mAbs (CasMabs) against PDPN, PMab-117 (rat IgM, kappa), by immunizing rats with PDPN-overexpressed glioblastoma cells. The recombinant mouse IgG2a-type PMab-117 (PMab-117-mG2a) reacted with the PDPN-positive tumor PC-10 and LN319 cells but not with PDPN-knockout LN319 cells in flow cytometry. PMab-117-mG2a did not react with normal kidney podocytes and normal epithelial cells from the lung bronchus, mammary gland, and corneal. In contrast, one of the non-CasMabs against PDPN, NZ-1, showed high reactivity to PDPN in both tumor and normal cells. Moreover, PMab-117-mG2a exerted antibody-dependent cellular cytotoxicity in the presence of effector splenocytes. In the human tumor xenograft models, PMab-117-mG2a exhibited potent antitumor effects. These results indicated that PMab-117-mG2a could be applied to antibody-based therapy against PDPN-expressing human tumors while reducing the adverse effects.

Keywords

cancer-specific monoclonal antibody; podoplanin; ADCC, mouse xenograft model

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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