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

Autor: Tomohiro Tanaka, Hiroyuki Suzuki, Tomokazu Ohishi, Mika K. Kaneko, Yukinari Kato
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cells, Vol 13, Iss 22, p 1833 (2024)
Druh dokumentu: article
ISSN: 13221833
2073-4409
DOI: 10.3390/cells13221833
Popis: Podoplanin (PDPN) overexpression is associated with poor clinical outcomes in various tumors. PDPN is involved in malignant tumor 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 a cancer-specific mAb (CasMab) 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.
Databáze: Directory of Open Access Journals
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