title: A novel fully human antitumour immunoRNase targeting ErbB2-positive tumours.
abstract: BACKGROUND
  ErbB2 is an attractive target for immunotherapy, as it is a tyrosine kinase receptor overexpressed on tumour cells of different origin, with a key role in the development of malignancy. Trastuzumab, the only humanised anti-ErbB2 antibody currently used in breast cancer with success, can engender cardiotoxicity and a high fraction of patients is resistant to Trastuzumab treatment.
  
  
  METHODS
  A novel human immunoRNase, called anti-ErbB2 human compact antibody-RNase (Erb-hcAb-RNase), made up of the compact anti-ErbB2 antibody Erbicin-human-compact Antibody (Erb-hcAb) and human pancreatic RNase (HP-RNase), has been designed, expressed in mammalian cell cultures and purified. The immunoRNase was then characterised as an enzymatic protein, and tested for its biological actions in vitro and in vivo on ErbB2-positive tumour cells.
  
  
  RESULTS
  Erb-hcAb-RNase retains the enzymatic activity of HP-RNase and specifically binds to ErbB2-positive cells with an affinity comparable with that of the parental Erb-hcAb. Moreover, this novel immunoRNase is endowed with an effective and selective antiproliferative action for ErbB2-positive tumour cells both in vitro and in vivo. Its antitumour activity is more potent than that of the parental Erb-hcAb as the novel immunoconjugate has acquired RNase-based cytotoxicity in addition to the inhibitory growth effects, antibody-dependent and complement-dependent cytotoxicity of Erb-hcAb.
  
  
  CONCLUSIONS
  Erb-hcAb-RNase could be a promising candidate for the immunotherapy of ErbB2-positive tumours.
authors.affiliation: Dipartimento di Biologia Strutturale e Funzionale, Università Federico II, via Cinthia, Napoli 80126, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Borriello
authors.forename: P
authors.initials: P
authors.lastname: Laccetti
authors.forename: G
authors.initials: G
authors.lastname: Terrazzano
authors.forename: G
authors.initials: G
authors.lastname: D'Alessio
authors.forename: C
authors.initials: C
authors.lastname: De Lorenzo
mesh_terms: D001943:Breast Neoplasms / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012259:Ribonuclease, Pancreatic / Q000276:immunology; D012260:Ribonucleases / Q000494:pharmacology
chemical_list: D018796:Immunoconjugates; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D012259:Ribonuclease, Pancreatic; D012260:Ribonucleases; C525747:Erb-hcAb; C508053:ERBB2 protein, human; C518070:ERB-hRNase