Monoclonal antibody C242-Pseudomonas exotoxin A. A specific and potent immunotoxin with antitumor activity on a human colon cancer xenograft in nude mice.
Two immunotoxins were constructed by chemically coupling the monoclonal antibody C242 to Pseudomonas exotoxin A (PE) or a modified form, NlysPE40, that lacks the cell binding domain of PE. Monoclonal antibody C242 recognizes a specific sialylated carbohydrate epitope on a high molecular weight membrane glycoprotein present on cells of human colon, pancreatic, and cervical cancers. C242-PE and C242-NlysPE40 were very cytotoxic for cells expressing this antigen with 50% inhibition of protein synthesis occurring on Colo205 cells at 0.2 ng/ml (0.9 pM) for C242-PE and 6.0 ng/ml (31 pM) for C242-NlysPE40. The two immunotoxins also exhibited a strong antitumor effect on a human colon cancer xenograft grown in nude mice. The specificity and potency of these two C242 immunotoxins warrant their further development for the treatment of cancer.
Debinski
W
W
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Karlsson
B
B
Lindholm
L
L
Siegall
C B
CB
Willingham
M C
MC
FitzGerald
D
D
Pastan
I
I
D036002:ADP Ribose Transferases; D000230:Adenocarcinoma / Q000628:therapy; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D000915:Antibody Affinity; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D001427:Bacterial Toxins; D001483:Base Sequence; D003110:Colonic Neoplasms / Q000628:therapy*; D005098:Exotoxins / Q000008:administration & dosage* / Q000633:toxicity; D006801:Humans; D007167:Immunotherapy; D000922:Immunotoxins / Q000737:chemistry*; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009368:Neoplasm Transplantation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011993:Recombinant Fusion Proteins; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A