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 sel ective 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 fusin g 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 an titumor potency of rhIL-9-ETA' was evaluated against the Hodgkin-deriv ed cell lines L540Cy, KM-H2 and L1236, the Burkitt lymphoma cell line Daudi, the erythroleukemia cell line K562, and the mastocytoma cell li ne P815-hIL9R, transfected with hIL-9 receptor cDNA. Recombinant hIL-9 -ETA' exhibited potent specific cytotoxic effects against P815-hIL9R, H562 and L1236 cells, inhibiting protein synthesis by 50% (IC50) at co ncentrations of 0.05, 0.58 and 3 mu g/ml respectively. The cytotoxic e ffect was abrogated after addition of polyclonal antibodies against th e human IL-9. rhIL-9-ETA' might be of potential use against hIL-9R-exp ressing malignancies.