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 can...

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Bibliographic Details
Published in:Bioconjugate chemistry 1990-07, Vol.1 (4), p.264-268
Main Authors: FitzGerald, David, Idziorek, Thierry, Batra, Janendra K, Willingham, Mark, Pastan, Ira
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - pharmacology
Antineoplastic Agents - pharmacology
Ascites - therapy
Breast Neoplasms - pathology
Breast Neoplasms - therapy
Cell Survival
Colonic Neoplasms - pathology
Colonic Neoplasms - therapy
Exotoxins - pharmacology
Female
Humans
Immunotoxins - administration & dosage
Immunotoxins - pharmacology
Mice
Mice, Nude
Neoplasm Proteins - biosynthesis
Neoplasm Transplantation
Ovarian Neoplasms - pathology
Ovarian Neoplasms - therapy
Pseudomonas
Sulfides - pharmacology
Time Factors
Tumor Cells, Cultured
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Summary: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.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc00004a006