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

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.
AuthorsE A Wolff, I Hellström, D F Chace, K E Hellström, C B Siegall
JournalTherapeutic immunology (Ther Immunol) Vol. 2 Issue 3 Pg. 137-45 (Jun 1995) ISSN: 0967-0149 [Print] ENGLAND
PMID8885132 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Exotoxins
  • Immunotoxins
  • LysPE40 exotoxin
  • Membrane Glycoproteins
  • PMEL protein, human
  • Proteins
  • Si protein, mouse
  • gp100 Melanoma Antigen
  • 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

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