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.
D036002:ADP Ribose Transferases; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001427:Bacterial Toxins; D001428:Bacterial Vaccines / Q000276:immunology*; D005098:Exotoxins / Q000276:immunology*; D006801:Humans; D000922:Immunotoxins / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D005098:Exotoxins; D000922:Immunotoxins; D008070:Lipopolysaccharides; D011135:Polysaccharides, Bacterial; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A