Item type |
文献 / Documents(1) |
公開日 |
2021-07-20 |
アクセス権 |
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アクセス権 |
open access |
資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
出版社版DOI |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.18632/oncotarget.5339 |
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言語 |
ja |
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関連名称 |
10.18632/oncotarget.5339 |
出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
タイトル |
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タイトル |
The chimeric antibody chLpMab-7 targeting human podoplanin suppresses pulmonary metastasis via ADCC and CDC rather than via its neutralizing activity |
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言語 |
en |
著者 |
カトウ, ユキナリ
クニタ, アキコ
阿部, 真治
オガサワラ, サトシ
フジイ, ユキ
オキ, ヒロハル
フカヤマ, マサシ
西岡, 安彦
カネコ, ミカ
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抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
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. |
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言語 |
en |
キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
podoplanin |
キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
PDPN |
キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
metastasis |
キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
monoclonal antibody |
キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
ADCC/CDC |
書誌情報 |
en : Oncotarget
巻 6,
号 34,
p. 36003-36018,
発行日 2015-09-25
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収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
19492553 |
出版者 |
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出版者 |
Impact Journals |
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言語 |
en |
EID |
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識別子 |
312296 |
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識別子タイプ |
URI |
言語 |
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言語 |
eng |