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Monoclon Antib Immunodiagn Immunother. 2017 Jun;36(3):104-112. doi: 10.1089/mab.2017.0014. Epub 2017 May 15.

ChLpMab-23: Cancer-Specific Human-Mouse Chimeric Anti-Podoplanin Antibody Exhibits Antitumor Activity via Antibody-Dependent Cellular Cytotoxicity.

Author information

1
1 Department of Antibody Drug Development, Tohoku University Graduate School of Medicine , Sendai, Japan .
2
2 Department of Regional Innovation, Tohoku University Graduate School of Medicine , Sendai, Japan .
3
3 Department of Pathology, Graduate School of Medicine, The University of Tokyo , Tokyo, Japan .
4
4 Department of Clinical Pharmacy Practice Pedagogy, Graduate School of Biomedical Sciences, Tokushima University , Tokushima, Japan .
5
5 Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University , Tokushima, Japan .
6
6 New Industry Creation Hatchery Center, Tohoku University, Sendai, Japan .

Abstract

Podoplanin is expressed in many cancers, including oral cancers and brain tumors. The interaction between podoplanin and its receptor C-type lectin-like receptor 2 (CLEC-2) has been reported to be involved in cancer metastasis and tumor malignancy. We previously established many monoclonal antibodies (mAbs) against human podoplanin using the cancer-specific mAb (CasMab) technology. LpMab-23 (IgG1, kappa), one of the mouse anti-podoplanin mAbs, was shown to be a CasMab. However, we have not shown the usefulness of LpMab-23 for antibody therapy against podoplanin-expressing cancers. In this study, we first determined the minimum epitope of LpMab-23 and revealed that Gly54-Leu64 peptide, especially Gly54, Thr55, Ser56, Glu57, Asp58, Arg59, Tyr60, and Leu64 of podoplanin, is a critical epitope of LpMab-23. We further produced human-mouse chimeric LpMab-23 (chLpMab-23) and investigated whether chLpMab-23 exerts antibody-dependent cellular cytotoxicity (ADCC) and antitumor activity. In flow cytometry, chLpMab-23 showed high sensitivity against a podoplanin-expressing glioblastoma cell line, LN319, and an oral cancer cell line, HSC-2. chLpMab-23 also showed ADCC activity against podoplanin-expressing CHO cells (CHO/podoplanin). In xenograft models with HSC-2 and CHO/podoplanin, chLpMab-23 exerts antitumor activity using human natural killer cells, indicating that chLpMab-23 could be useful for antibody therapy against podoplanin-expressing cancers.

KEYWORDS:

ADCC; CDC; antitumor activity; monoclonal antibody; podoplanin

PMID:
28504613
DOI:
10.1089/mab.2017.0014
[Indexed for MEDLINE]

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