Antibodies reacting with human ovarian cancer cells have been coupled to Pseudomonas toxin. Such immunotoxins kill ovarian cancer cells in tissue culture and human ovarian cancer cells growing in the peritoneal cavity of nude mice. Two new monoclonal antibodies reacting with ovarian cancer cells have been isolated: OVB1 and OVB3. OVB3 reacts with a small number of human tissues and OVB3-PE is active in an animal model. OVB3-PE is being prepared for a human trial in patients with ovarian cancer. The function of the three structural domains of PE has been defined by deletion mapping using a T7 promoter to express the gene in E. coli. Domain I is the cell recognition domain, domain II is the translocating domain and domain III is the ADP ribosylating domain. Domain I has been deleted and replaced by a cDNA for TGF alpha. The chimeric protein produced kills EGF receptor bearing cells. Phase I studies have begun in collaboration with T. Waldmann to treat adult T-cell leukemia with an antibody to the IL2 receptor (anti-Tac) conjugated to Pseudomonas exotoxin.
