Antitumour activity of a melanoma-specific immunotoxin, ME20-LysPE40.

Abstract

An immunotoxin conjugate has been prepared by linking an internalizing antibody with melanoma selectivity, ME20, with a binding-defective form of Pseudomonas exotoxin A, LysPE40. ME20-LysPE40 binds to a 105,000 Da cell-surface antigen present on melanoma cells (ME20-M) within twofold of unmodified ME20 and was cytotoxic to two human melanoma cell lines, H3606 and MALME-3M, with EC50 values of 100 and 200 pM, respectively. Immunotoxin treatment, initiated 1 day following subcutaneous implantation of H3606 melanoma cells into mice, prevented outgrowth of tumour xenografts in > 50% of the mice. In contrast, only a modest inhibition in tumour growth was observed if the immunotoxin was administered 5 days after implantation of in vivo passaged H3606 tumour fragments in mice. This study shows that the internalizing monoclonal antibody ME20 IgG can be used for targeting a toxin toward melanoma cells displaying the ME20-M antigen.

• Authors: E A Wolff, I Hellström, D F Chace, K E Hellström, C B Siegall
• Journal: Therapeutic immunology (Ther Immunol) Vol. 2 Issue 3 Pg. 137-45 (Jun 1995) ISSN: 0967-0149 [Print] England
• PMID: 8885132 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antigens, Neoplasm
• Exotoxins
• Immunotoxins
• LysPE40 exotoxin
• Membrane Glycoproteins
• PMEL protein, human
• Pmel protein, mouse
• Proteins
• gp100 Melanoma Antigen

Topics

• Animals
• Antibodies, Monoclonal (immunology, metabolism, therapeutic use)
• Antigens, Neoplasm (immunology)
• Cell Death
• Exotoxins (immunology, therapeutic use)
• Female
• Immunotoxins (chemistry, therapeutic use)
• Melanoma (immunology, pathology, therapy)
• Membrane Glycoproteins (immunology)
• Mice
• Mice, Nude
• Proteins
• Tumor Cells, Cultured (drug effects, metabolism, pathology)
• gp100 Melanoma Antigen