抗体依赖性细胞介导的细胞毒性
Glypican 3型
单克隆抗体
表位
抗体
细胞毒性
分子生物学
癌症研究
肝细胞癌
化学
生物
免疫学
生物化学
体外
作者
Kiyotaka Nakano,Tetsuro Orita,Junichi Nezu,Takeshi Yoshino,Iwao Ohizumi,Masamichi Sugimoto,Koh Furugaki,Yasuko Kinoshita,Takahiro Ishiguro,Takao Hamakubo,Tatsuhiko Kodama,Hiroyuki Aburatani,Hisafumi Yamada‐Okabe,Masayuki Tsuchiya
标识
DOI:10.1016/j.bbrc.2008.11.033
摘要
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.
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