title: A new human antitumor immunoreagent specific for ErbB2.
abstract: OBJECTIVE
  Our aim was to isolate a novel human mini-antibody(scFv) that specifically targets ErbB2-positive cancer cells. ErbB2, a tyrosinekinase receptor, is overexpressed in clinically significant tumors, such as breast, ovary, and lung carcinomas. In normal tissues, it is expressed only in certain epithelial cell types.
  
  
  METHODS
  A large phagemid library (Griffin.1 library) of human scFv was used for the isolation of the ErbB2-specific scFv. A very effective strategy was developed for the isolation, consisting in a double subtractive selection, the use of two different combinations of "positive," i.e., ErbB2-bearing, and "negative" cell lines.
  
  
  RESULTS
  Here we report the isolation of the first human anti-ErbB2 mini-antibody endowed with antitumor action. Both in its soluble and phage format, it binds specifically to ErbB2, inhibits its autophosphorylation, is internalized by target cells, and exerts a strong and specific antiproliferative action on ErbB2-positive target cells. A correlation was found between the extent of this antiproliferative effect and the expression levels of ErbB2 on target cells, with a strong cytotoxicity for hyper-expressing cells, such as SKBR3, in which apoptosis was evidenced.
  
  
  CONCLUSIONS
  This scFv is a potentially effective immunoreagent for diagnostics and therapeutics of certain cancers, both as a readily diffused molecule in solid tumors and as an essential asset for the construction of fully human anticancer drugs.
authors.affiliation: Department of Biological Chemistry, University of Naples Federico II, via Mezzocannone 16, 80134 Naples, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: De Lorenzo
authors.forename: Donald B
authors.initials: DB
authors.lastname: Palmer
authors.forename: Renata
authors.initials: R
authors.lastname: Piccoli
authors.forename: Mary A
authors.initials: MA
authors.lastname: Ritter
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Alessio
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001435:Bacteriophages / Q000235:genetics; D001943:Breast Neoplasms / Q000628:therapy*; D002455:Cell Division / Q000187:drug effects; D003001:Cloning, Molecular; D004705:Endocytosis; D005260:Female; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000276:immunology; D051379:Mice; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000166:cytology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D007135:Immunoglobulin Variable Region; D018719:Erb-b2 Receptor Tyrosine Kinases; D014443:Tyrosine