Recombinant pseudomonas exotoxin: construction of an active...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/62 (2006.01) A61K 39/104 (2006.01) A61K 47/48 (2006.01) C07K 14/21 (2006.01) C07K 14/495 (2006.01) C07K 14/55 (2006.01) C07K 16/28 (2006.01) C12N 9/24 (2006.01) C12N 15/16 (2006.01) C12N 15/24 (2006.01) C12N 15/31 (2006.01) C12N 15/56 (2006.01) A61K 38/00 (2006.01) A61K 39/00 (2006.01)

Patent

CA 1336691

Large amounts of various modified forms of Pseudomonas exotoxin are produced. At least one of the modified forms (pJH8) of the exotoxin exhibits low toxicity to human or mouse cells by itself but retains its enzymatic activity and makes a very active cell specific immunotoxin with very low nonspecific cytotoxicity. All the constructs with low cytotoxic activity will be useful as vaccines to produce the antibodies to treat pseudomonas sepsis. In addition, the protein encoded by domain I alone could be administered directly to patients to treat pseudomonas sepsis because that domain would block toxin binding to cells. Clones containing domain II and particularly clone pJH12 can be fused to other toxins which have low activity (such as ricin A chain or pokeweed antiviral protein) to increase cell-killing activity without increasing their nonspecific binding to cells.

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