Construction of immunotoxins using Pseudomonas exotoxin A.

The above methodology has been used to prepare a variety of PE-immunotoxins. These reagents are potent cytotoxic agents for cells in culture that bind the appropriate antibody and nontoxic when cells do not bind the antibody. PE-immunotoxins can be used to select for mutant cultured cells which lack the target of the antibody (see chapter by Gottesman [9] on drug-resistant mutants). Recently, we have also demonstrated in vivo activity when a PE-immunotoxin was used to inhibit the growth of human ovarian cancer cells in a nude mouse model of ovarian cancer. Also PE-immunotoxins are currently being evaluated in Phase 1 clinical trials for the treatment of adult T-cell leukemia.