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.
Wolff
E A
EA
Bristol-Myers Squibb, Pharmaceutical Research Institute, Seattle, Washington 98121, USA.
Hellström
I
I
Chace
D F
DF
Hellström
K E
KE
Siegall
C B
CB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology; D016923:Cell Death; D005098:Exotoxins / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D000922:Immunotoxins / Q000737:chemistry / Q000627:therapeutic use*; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D011506:Proteins; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058951:gp100 Melanoma Antigen
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D005098:Exotoxins; D000922:Immunotoxins; C062218:LysPE40 exotoxin; D008562:Membrane Glycoproteins; C548637:PMEL protein, human; C548642:Pmel protein, mouse; D011506:Proteins; D058951:gp100 Melanoma Antigen