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: Pamela J Russell, Dean Hewish, Teresa Carter, Katy Sterling-Levis, Kim Ow, Meghan Hattarki, Larissa Doughty, Robin Guthrie, Deborah Shapira, Peter L Molloy, Jerome A Werkmeister, Alexander A Kortt
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 53 Issue 5 Pg. 411-21 (May 2004) ISSN: 0340-7004 [Print] Germany
• PMID: 14722668 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antigens, Neoplasm
• Cross-Linking Reagents
• Immunoconjugates
• J591 monoclonal antibody
• Peptide Fragments
• Succinimides
• Melitten
• N-succinimidyl 3-(2-pyridyldithio)propionate

Topics

• Animals
• Antibodies, Monoclonal (pharmacokinetics, therapeutic use)
• Antigens, Neoplasm (immunology)
• Cell Division
• Cross-Linking Reagents
• Cytotoxicity, Immunologic (drug effects)
• Flow Cytometry
• Humans
• Immunoconjugates (therapeutic use)
• In Vitro Techniques
• Male
• Melitten (pharmacokinetics, therapeutic use)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasms, Experimental (drug therapy, metabolism)
• Peptide Fragments (pharmacokinetics, therapeutic use)
• Prostatic Neoplasms (drug therapy, metabolism, mortality)
• Succinimides
• Survival Rate
• Tumor Cells, Cultured