Klimka A, Barth S, Drillich S, Wels W, van Snick J, Renauld J C, Tesch H, Bohlen H, Diehl V, Engert A
Medizinische Universitätsklinik I, Cologne, Germany.
Cytokines Mol Ther. 1996 Sep;2(3):139-46.
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.
人白细胞介素-9（hIL-9）受体可能是选择性免疫治疗的靶点。它在多种恶性细胞上表达，包括霍奇金淋巴瘤、非霍奇金淋巴瘤和急性髓性白血病（AML）。因此，我们通过将hIL-9-cDNA与修饰的铜绿假单胞菌外毒素A（ETA'）融合构建了一种新的嵌合毒素。在表达hIL-9受体的不同细胞系上评估了新重组蛋白rhIL-9-ETA'的结合特性。针对转染了hIL-9受体cDNA的霍奇金来源的细胞系L540Cy、KM-H2和L1236、伯基特淋巴瘤细胞系Daudi、红白血病细胞系K562以及肥大细胞瘤细胞系P815-hIL9R，评估了rhIL-9-ETA'的抗肿瘤效力。重组hIL-9-ETA'对P815-hIL9R、K562和L1236细胞表现出强大的特异性细胞毒性作用，分别在浓度为0.05、0.58和3微克/毫升时抑制蛋白质合成达50%（IC50）。加入抗人IL-9的多克隆抗体后，细胞毒性作用消失。rhIL-9-ETA'可能对表达hIL-9R的恶性肿瘤有潜在用途。
