Topp M S, Papadimitriou C A, Eitelbach F, Koenigsmann M, Oelmann E, Koehler B, Oberberg D, Reufi B, Stein H, Thiel E
Department of Hematology and Oncology, Klinikum Steglitz, Freie Universitaet Berlin, Germany.
Cancer Res. 1995 May 15;55(10):2173-6.
Interleukin 4, a T cell-derived 20-kDa glycoprotein, plays an important role in regulating the immune response of B cells, T cells, and macrophages against infections and malignant cells. For this reason recombinant human interleukin 4 (rhIL-4) has entered early clinical trials in cancer patients. In the present study we report that rhIL-4 has an antiproliferative effect on five of nine cell lines derived from human colon tumors, head and neck tumors, and glioblastomas as measured by a decrease of colony formation in human tumor cloning assays. All of the cell lines with in vitro responsiveness express at least 100 high-affinity receptors for human interleukin 4 per cell on their cell surface, whereas the nonresponsive tumor cell lines lack expression of high-affinity receptors for human interleukin 4 on their cell surface. In the next series of experiments we have xenotransplanted some of the responsive cell lines into athymic nude mice. Subsequently, the animals were treated s.c. twice daily with 0.5 mg/m2 rhIL-4 or control vehicle for at least 12 days. There was a clear growth inhibition of these xenotransplanted tumors in the mice treated with rhIL-4. Histology of the tumors in both groups revealed no marked infiltration with murine hematopoietic and lymphocytic cells as evaluated by staining with a rat anti-mouse CD45 antibody. We conclude that rhIL-4 has a direct therapeutic activity on the growth of some human epithelial and nonepithelial tumor cell lines which, along with its regulatory function on hematolymphopoietic cells, makes this cytokine an interesting candidate for experimental tumor therapy.
白细胞介素4是一种由T细胞产生的20 kDa糖蛋白，在调节B细胞、T细胞和巨噬细胞针对感染和恶性细胞的免疫反应中发挥重要作用。因此，重组人白细胞介素4（rhIL-4）已进入癌症患者的早期临床试验。在本研究中，我们报告称，通过人肿瘤克隆试验中集落形成的减少来衡量，rhIL-4对源自人结肠肿瘤、头颈部肿瘤和胶质母细胞瘤的9种细胞系中的5种具有抗增殖作用。所有具有体外反应性的细胞系在其细胞表面每细胞至少表达100个人白细胞介素4的高亲和力受体，而无反应的肿瘤细胞系在其细胞表面缺乏人白细胞介素4高亲和力受体的表达。在接下来的一系列实验中，我们将一些有反应的细胞系异种移植到无胸腺裸鼠体内。随后，每天两次给动物皮下注射0.5 mg/m2 rhIL-4或对照载体，持续至少12天。用rhIL-4治疗的小鼠中，这些异种移植肿瘤有明显的生长抑制。用大鼠抗小鼠CD45抗体染色评估，两组肿瘤的组织学均显示没有明显的小鼠造血和淋巴细胞浸润。我们得出结论，rhIL-4对一些人上皮和非上皮肿瘤细胞系的生长具有直接治疗活性，这与其对血液淋巴细胞的调节功能一起，使这种细胞因子成为实验性肿瘤治疗的一个有吸引力的候选者。
