title: Cytotoxic properties of immunoconjugates containing melittin-like peptide 101 against prostate cancer: in vitro and in vivo studies.
abstract: BACKGROUND
  Monoclonal antibodies (MAbs) can target therapy to tumours while minimising normal tissue exposure. Efficacy of immunoconjugates containing peptide 101, designed around the first 22 amino acids of bee venom, melittin, to maintain the amphipathic helix, to enhance water solubility, and to increase hemolytic activity, was assessed in nude mice bearing subcutaneous human prostate cancer xenografts.
  
  
  METHODS
  Mouse MAbs, J591 and BLCA-38, which recognise human prostate cancer cells, were cross-linked to peptide 101 using SPDP. Tumour-bearing mice were used to compare biodistributions of radiolabeled immunoconjugates and MAb, or received multiple sequential injections of immunoconjugates. Therapeutic efficacy was assessed by delay in tumour growth and increased mouse survival.
  
  
  RESULTS
  Radiolabeled immunoconjugates and antibodies showed similar xenograft tropism. Systemic or intratumoural injection of immunoconjugates inhibited tumour growth in mice relative to carrier alone, unconjugated antibody and nonspecific antibody-peptide conjugates and improved survival for treated mice.
  
  
  CONCLUSIONS
  Immunoconjugates deliver beneficial effects; further peptide modifications may increase cytotoxicity.
authors.affiliation: Oncology Research Centre, Department of Clinical Medicine, Prince of Wales Hospital, University of New South Wales, NSW 2031 Randwick, Australia. p.Russell@unsw.edu.au
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Russell
authors.forename: Dean
authors.initials: D
authors.lastname: Hewish
authors.forename: Teresa
authors.initials: T
authors.lastname: Carter
authors.forename: Katy
authors.initials: K
authors.lastname: Sterling-Levis
authors.forename: Kim
authors.initials: K
authors.lastname: Ow
authors.forename: Meghan
authors.initials: M
authors.lastname: Hattarki
authors.forename: Larissa
authors.initials: L
authors.lastname: Doughty
authors.forename: Robin
authors.initials: R
authors.lastname: Guthrie
authors.forename: Deborah
authors.initials: D
authors.lastname: Shapira
authors.forename: Peter L
authors.initials: PL
authors.lastname: Molloy
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Werkmeister
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Kortt
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology; D002455:Cell Division; D003432:Cross-Linking Reagents; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008297:Male; D008555:Melitten / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D010446:Peptide Fragments / Q000493:pharmacokinetics / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D013388:Succinimides; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D003432:Cross-Linking Reagents; D018796:Immunoconjugates; C478680:J591 monoclonal antibody; D010446:Peptide Fragments; D013388:Succinimides; D008555:Melitten; C018151:N-succinimidyl 3-(2-pyridyldithio)propionate