The chimeric antibody chLpMab-7 targeting human podoplanin suppresses pulmonary metastasis via ADCC and CDC rather than via its neutralizing activity

• Kato, Yukinari

• Kunita, Akiko

• Abe, Shinji

• Ogasawara, Satoshi

• Fujii, Yuki

• Oki, Hiroharu

• Fukayama, Masashi

• Nishioka, Yasuhiko

• Kaneko, Mika K.

抄録

Podoplanin (PDPN/Aggrus/T1α) binds to C-type lectin-like receptor-2 (CLEC-2) and induces platelet aggregation. PDPN is associated with malignant progression, tumor metastasis, and poor prognosis in several types of cancer. Although many anti-human PDPN (hPDPN) monoclonal antibodies (mAbs), such as D2-40 and NZ-1, have been established, these epitopes are limited to the platelet aggregation-stimulating (PLAG) domain (amino acids 29-54) of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-7, which is more sensitive than D2-40 and NZ-1, using the Cancer-specific mAb (CasMab) method. The epitope of LpMab-7 was shown to be entirely different from that of NZ-1, a neutralizing mAb against the PLAG domain according to an inhibition assay and lectin microarray analysis. In the present study, we produced a mouse-human chimeric anti-hPDPN mAb, chLpMab-7. ChLpMab-7 showed high antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Furthermore, chLpMab-7 inhibited the growth of hPDPN-expressing tumors in vivo. Although chLpMab-7 recognizes a non-PLAG domain of hPDPN, it suppressed the hematogenous metastasis of hPDPN-expressing tumors. These results indicated that chLpMab-7 suppressed tumor development and hematogenous metastasis in a neutralization-independent manner. In conclusion, hPDPN shows promise as a target in the development of a novel antibody-based therapy.

収録刊行物

• Oncotarget

  Oncotarget 6 (34), 36003-36018, 2015-09-25

  Impact Journals

キーワード

• podoplanin
• PDPN
• metastasis
• monoclonal antibody
• ADCC/CDC

詳細情報

• CRID: 1050288834686138112
• NII論文ID: 120007120171
• ISSN: 19492553
• Web Site: http://repo.lib.tokushima-u.ac.jp/115672
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
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  • CiNii Articles