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Anti-glypican 3 antibodies cause ADCC against human hepatocellular carcinoma cells.

Abstract：

:Glypican 3 (GPC3), a GPI-anchored heparan sulfate proteoglycan, is expressed in the majority of hepatocellular carcinoma (HCC) tissues. Using MRL/lpr mice, we successfully generated a series of anti-GPC3 monoclonal antibodies (mAbs). GPC3 was partially cleaved between Arg358 and Ser359, generating a C-terminal 30-kDa fragment and an N-terminal 40-kDa fragment. All mAbs that induced antibody-dependent cellular cytotoxicity (ADCC) and/or complement-dependent cytotoxicity (CDC) against cells expressing GPC3 recognized the 30-kDa fragment, indicating that the C-terminal region of GPC3 serves as an epitope for mAb with ADCC and/or CDC inducing activities. Chimeric mAbs with Fc replaced by human IgG1 were created from GC33, one of the mAbs that reacted with the C-terminal 30-kDa fragment. Chimeric GC33 induced not only ADCC against GPC3-positive human HCC cells but also was efficacious against the Huh-7 human HCC xenograft. Thus, mAbs against the C-terminal 30-kDa fragment such as GC33 are useful in therapy targeting HCC.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Nakano K,Orita T,Nezu J,Yoshino T,Ohizumi I,Sugimoto M,Furugaki K,Kinoshita Y,Ishiguro T,Hamakubo T,Kodama T,Aburatani H,Yamada-Okabe H,Tsuchiya M

doi

10.1016/j.bbrc.2008.11.033

subject

Has Abstract

pub_date

2009-01-09 00:00:00

pages

279-84

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(08)02229-8

journal_volume

378

pub_type

杂志文章

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