論文 - 詳細
| RRC ID | 61592 |
|---|---|
| 著者 | Shinohara H, Morita S, Kawai M, Miyamoto A, Sonoda T, Pastan I, Tanigawa N. |
| タイトル | Expression of HER2 in human gastric cancer cells directly correlates with antitumor activity of a recombinant disulfide-stabilized anti-HER2 immunotoxin. |
| ジャーナル | J Surg Res |
| Abstract |
BACKGROUND:Amplification of the human epidermal growth factor receptor 2 (HER2) gene and overexpression of the HER2 protein have been associated with an unfavorable prognosis. We determined the efficacy of an anti-HER2 immunotoxin, erb-38 [e23(dsFv)PE38], against human gastric cancer cells. METHODS:Immunotoxin was made by fusing the disulfide-stabilized Fv fragments (dsFv) of a monoclonal antibody e23 to a truncated mutant of M(r) 38 Pseudomonas exotoxin (PE38) that lacks its cell-binding domain. RESULTS:The immunotoxin-mediated cytotoxicity directly correlated with the expression levels of the HER2 gene and protein in human gastric cancer cells. Interestingly, MKN-45P cells, a variant line of MKN-45 producing peritoneal dissemination and ascites in vivo, expressed a higher level of HER2 and were more sensitive to erb-38 than MKN-45 cells. RFB-4, a control anti-CD22 immunotoxin, was cytotoxic against none of the tested human gastric cancer cells, also suggesting that the lysis mediated by erb-38 was specific for HER2 expression. Three consecutive iv injections of erb-38 at doses of 0.5 or 5 microg/body eradicated experimental liver metastases and peritoneal disseminations produced by MKN-45P in a dose-dependent manner. CONCLUSIONS:We conclude that an erb-38 anti-HER2 immunotoxin has specific antitumor activities against human gastric cancer cells overexpressing HER2. |
| 巻・号 | 102(2) |
| ページ | 169-77 |
| 公開日 | 2002-2-1 |
| DOI | 10.1006/jsre.2001.6305 |
| PII | S002248040196305X |
| PMID | 11796015 |
| MeSH | Animals Ascites / drug therapy Disulfides Gene Expression Regulation, Neoplastic* Humans Immunotoxins / pharmacology* Liver Neoplasms, Experimental / drug therapy Liver Neoplasms, Experimental / secondary Male Mice Mice, Nude Receptor, ErbB-2 / genetics* Stomach Neoplasms / drug therapy* Stomach Neoplasms / pathology Stomach Neoplasms / physiopathology Tumor Cells, Cultured / drug effects Tumor Cells, Cultured / physiology Tumor Cells, Cultured / transplantation Xenograft Model Antitumor Assays |
| IF | 1.841 |
| リソース情報 | |
| ヒト・動物細胞 | MKN45(RCB1001) MKN74(RCB1002) |