Use of Pseudomonas aeruginosa toxin A in the construction of conjugate vaccines and immunotoxins.

Pseudomonas aeruginosa toxin A was used to construct conjugate vaccines and potent cytotoxic immunotoxins. Nontoxic, serologically active O polysaccharide derived from P. aeruginosa lipopolysaccharide (LPS) was covalently coupled to toxin A via reductive amination. The conjugate was nontoxic, nonpyrogenic, and had a molecular size of 2 X 10(6). The conjugate vaccine was safe when administered to human volunteers and was capable of evoking an immune response to both LPS and toxin A. Native toxin A was coupled to monoclonal antibodies to the human transferrin receptor and the human interleukin 2 receptor to produce immunotoxins active against receptor-bearing cell lines. Antitumor activity was demonstrated when the immunotoxin directed against the transferrin receptor was administered to nude mice bearing human ovarian tumors.