ANTI-PROSTATE IMMUNOTOXINS - CYTOTOXICITY OF E4 ANTIBODY-PSEUDOMONAS EXOTOXIN CONSTRUCTS

E4 is a monoclonal antibody (MAb) that reacts with a surface antigen p resent on normal prostate and prostate cancers. Using this antibody, 2 immunotoxins were generated, one being a chemical conjugate with a mu tant truncated form of Pseudomonas exotoxin A (PE), E4-PE35KDEL. The o ther is a recombinant single chain immunotoxin, E4(FV)PE38KDEL. The af finity of the conjugated immunotoxin was similar to the hybridoma-prod uced MAb E4, revealing that conjugation did not impair the binding abi lity. The affinity of the recombinant immunotoxin (10 nM) was 10-fold lower than that of the MAb, probably reflecting differences of bivalen t (MAb) vs, monovalent (Fv) binding. Antigen positive prostate, breast and colon carcinoma cell lines showed cytotoxic response to the E4 im munotoxins while antigen negative cells were not affected. The ICS, va lue, representing a 50% inhibition of cellular protein synthesis, rang ed from 0.3 to 20 ng/ml for E4-PE35KDEL and from 2 to 100 ng/ml for E4 (FV)-PE38KDEL. Therefore, the E4-derived immunotoxins may be useful fo r the treatment of prostate as well as breast and colon cancers.