Document Detail


Targeted killing of squamous carcinoma cells by a monoclonal antibody-peplomycin conjugate which recognizes the EGF receptor.
MedLine Citation:
PMID:  1723259     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We determined in vitro the antitumor activity of a conjugate prepared by binding a monoclonal antibody (B4G7), which recognizes the human epidermal growth factor (EGF) receptor, with peplomycin (PEP), which is an antitumor agent effective against squamous cell carcinoma. This B4G7-PEP conjugate was prepared by coupling of B4G7 and carboxymethylpeplomycin active ester. The conjugate killed A431 cells of squamous cell carcinoma which overexpress EGF receptors at lower concentrations than PEP alone. On the basis of its IC50, the conjugate was six times more potent than PEP alone. A simple mixture of B4G7 and PEP was as effective as PEP alone in cytotoxicity. The addition of ten times the amounts of B4G7 to this conjugate decreased its cytotoxicity. When other squamous cell carcinoma cell lines with different levels of EGF receptors (NA, Ca9-22, TE-1, TE-8) were treated with the conjugate, cells were killed dose-dependently and the cytotoxicity was dependent on the number of EGF receptors. When each squamous cell carcinoma cell line was treated with a control conjugate prepared by combining PEP with mouse IgG instead of B4G7, no cytotoxicity was observed. These results indicate that B4G7-PEP will be a useful weapon in multidisciplinary treatment which utilizes the EGF receptor, as these receptors are detected in a higher incidence in squamous cell carcinoma.
Authors:
M Osaku; M Ueda; N Ando; Y Shinozawa; N Hirota; N Shimizu; O Abe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  11     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    1991 Nov-Dec
Date Detail:
Created Date:  1992-02-28     Completed Date:  1992-02-28     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  GREECE    
Other Details:
Languages:  eng     Pagination:  1951-6     Citation Subset:  IM    
Affiliation:
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Antibiotics, Antineoplastic / therapeutic use*
Antibodies, Monoclonal / therapeutic use
Bleomycin / therapeutic use*
Carcinoma, Squamous Cell / metabolism,  therapy*
Cell Survival
Drug Screening Assays, Antitumor
Humans
Immunotoxins / therapeutic use*
Peplomycin
Receptor, Epidermal Growth Factor / metabolism*
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Antibodies, Monoclonal; 0/Immunotoxins; 11056-06-7/Bleomycin; 68247-85-8/Peplomycin; EC 2.7.10.1/Receptor, Epidermal Growth Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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