Antitumor activity of a thioether-linked immunotoxin: OVB3-PE.
A thioether-linked immunotoxin was made between Pseudomonas exotoxin and the monoclonal antibody OVB3. This conjugate, OVB3-PE, was cytotoxic for the human ovarium cancer cell line OVCAR-3 (ID of 2.5 x 10(-12) M) and it was therefore tested for antitumor activity in a nude mouse model of ovarian cancer. This model employs the injection of a lethal number of OVCAR-3 cells into the peritoneal cavity of nude mice. When 0.2-1 micrograms of OVB3-PE was injected intraperitoneally on three successive days beginning 3-5 days after OVCAR-3 cell implantation, the survival of the tumor-bearing mice was increased 2-4-fold compared to that of untreated control mice. Median survival times for control mice ranged from 44 to 50 days while survival times of 150 days or greater were seen in mice treated with OVB3-PE. When OVB3-PE administration was delayed until 2-4 weeks after tumor cell implantation, OVB3-PE treatment also showed antitumor activity, but the duration of survival was less than with the early treatments. OVB3-PE was also cytotoxic for MCF-7 breast carcinoma cells, HT-29 colon carcinoma cells, and A431 epidermoid carcinoma cells.
FitzGerald
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Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Idziorek
T
T
Batra
J K
JK
Willingham
M
M
Pastan
I
I
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001201:Ascites / Q000628:therapy; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000473:pathology / Q000628:therapy; D005098:Exotoxins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000473:pathology / Q000628:therapy; D011549:Pseudomonas; D013440:Sulfides / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D005098:Exotoxins; D000922:Immunotoxins; D009363:Neoplasm Proteins; D013440:Sulfides