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Interleukin‐4 receptors expressed on tumor cells may serve as a target for anticancer therapy using chimeric Pseudomonas exotoxin
Author(s) -
Debinski Waldemar,
Puri Raj K.,
Pastan Ira
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910580520
Subject(s) - pseudomonas exotoxin , receptor , cancer research , exotoxin , biology , medicine , immunology , microbiology and biotechnology , biochemistry , toxin , in vitro , cytotoxicity
Interleukin‐4 receptors (IL4R) are present on a wide variety of human cancer cells derived from both hematopoietic and epithelial malignancies. We have targeted IL4R on a human solid tumor xenograft with chimeric proteins composed of human IL4 (hIL4) and 2 different mutant forms of a powerful bacterial toxin, Pseudomonas exetoxin A (PE). The 2 chimeric toxins, termed hIL4‐PE 4E and hIL4‐PE38QQR, showed specific, hIL4R‐dependent and dose‐dependent antitumor activities. Neither of the chimeric toxins showed antitumor potency when the ADP‐ribosylation activity of the toxin was inactivated by mutagenesis. One of the chimeras, hIL4‐PE3BQQR, caused a complete although transient regression of established solid tumors. These observations indicate that hIL4‐PE chimeric proteins should be further evaluated for the treatment of human malignancies.