A deletion mutant of Pseudomonas exotoxin-A fused to recombinant human interleukin-9 (rhIL-9-ETA') shows specific cytotoxicity against IL-9-receptor-expressing cell lines.
The receptor for human interleukin-9 (hIL-9) might be a target for selective immunotherapy. It is expressed on a variety of malignant cells, including Hodgkin's lymphoma, non-Hodgkin lymphoma and acute myeloid leukemia (AML). We therefore constructed a new chimeric toxin by fusing hIL-9-cDNA to modified Pseudomonas aeruginosa exotoxin A (ETA'). The binding properties of the new recombinant protein, rhIL-9-ETA', were assessed on different cell lines expressing the hIL-9 receptor. The antitumor potency of rhIL-9-ETA' was evaluated against the Hodgkin-derived cell lines L540Cy, KM-H2 and L1236, the Burkitt lymphoma cell line Daudi, the erythroleukemia cell line K562, and the mastocytoma cell line P815-hIL9R, transfected with hIL-9 receptor cDNA. Recombinant hIL-9-ETA' exhibited potent specific cytotoxic effects against P815-hIL9R, K562 and L1236 cells, inhibiting protein synthesis by 50% (IC50) at concentrations of 0.05, 0.58 and 3 micrograms/ml respectively. The cytotoxic effect was abrogated after addition of polyclonal antibodies against the human IL-9. rhIL-9-ETA' might be of potential use against hIL-9R-expressing malignancies.
Klimka
A
A
Medizinische Universitätsklinik I, Cologne, Germany.
Barth
S
S
Drillich
S
S
Wels
W
W
van Snick
J
J
Renauld
J C
JC
Tesch
H
H
Bohlen
H
H
Diehl
V
V
Engert
A
A
D036002:ADP Ribose Transferases; D000818:Animals; D001427:Bacterial Toxins; D002051:Burkitt Lymphoma; D002470:Cell Survival / Q000187:drug effects; D019976:Cloning, Organism; D004926:Escherichia coli; D005098:Exotoxins / Q000096:biosynthesis / Q000633:toxicity*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D000922:Immunotoxins / Q000633:toxicity*; D016906:Interleukin-9 / Q000096:biosynthesis / Q000633:toxicity*; D012515:Mast-Cell Sarcoma; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D011550:Pseudomonas aeruginosa; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000502:physiology*; D053651:Receptors, Interleukin-9; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000633:toxicity; D011994:Recombinant Proteins / Q000096:biosynthesis; D017384:Sequence Deletion; D014162:Transfection; D014407:Tumor Cells, Cultured; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; D016906:Interleukin-9; D018123:Receptors, Interleukin; D053651:Receptors, Interleukin-9; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C508045:IL9R protein, human