INTERLEUKIN-4 AND THEIR RECEPTORS IN TUMOR BIOLOGY AND AIDS

我们发现多种人类实体肿瘤细胞表达 白介素4受体(IL-4R)此外，IL-4R被上调 人类Burkitt淋巴瘤(Raji)细胞株上的HIV调控基因TAT。 研究的特征是：a.功能意义 IL-4R在人体实体肿瘤和血液系统肿瘤中的表达及结构 靶向假单胞菌内毒素(PE)的研究C.IL-4R的作用机制 受HIV-TAT基因的调控。 A.肿瘤细胞上IL-4受体的结构和功能。IL-4引起 组织培养中对肿瘤细胞生长的抑制及其抑制作用 在不同的人类肿瘤中有不同程度的改变。相比之下，IL-4 对正常人血管内皮细胞的生长有适度的刺激作用 成纤维细胞系。人肾癌(RCC)细胞最多 对IL-4的生长抑制作用敏感。实验正在进行中 确定IL-4R其他功能的进展(例如，对人类白细胞抗原的调节 抗原、IL-4R和细胞因子的产生)。在……里面 初步实验表明，IL-4R的结构和性质似乎 在肾癌和人B细胞来源的淋巴瘤细胞系中相似。在这两个地方 细胞类型IL-4R似乎是内化和循环的。IL-2的结构 4R和其他亚单位(S)与IL-4R结合的可能性正在进行中 通过交联和免疫沉淀实验探索使用抗- IL-4R抗体。 B.IL-4R定向靶向一种假单胞菌外毒素。白介素4R 以嵌合蛋白为靶点在人肿瘤细胞上表达 由IL-4和PE组成。该蛋白对IL-4R具有高度的细胞毒作用 然而，阳性的肿瘤细胞，如外周血等正常细胞 淋巴细胞、内皮细胞和成纤维细胞对 IL-4-PE的细胞毒作用。正在进行研究，以检查反 该嵌合蛋白抗多种人肿瘤特性的研究 癌症。

We have discovered that a variety of human solid tumor cells express Interleukin-4 Receptors (IL-4R). In addition, IL-4R are upregulated by HIV regulatory gene tat on human Burkitt's lymphoma (Raji) cell line. Studies were carried out to characterize: A. the functional significance and structure of IL-4R on human solid and hematologic tumors; B. IL-4R directed targeting of a Pseudomonas endotoxin (PE); C. Mechanism of IL-4R regulation by HIV-tat gene. A. Structure and Function of IL-4 receptors on tumor cells. IL-4 caused the inhibition of tumor cell growth in tissue culture and this inhibition was of different degrees in different human tumors. In contrast, IL-4 caused modest stimulation of growth in normal human endothelial and fibroblast cell lines. Human renal cell carcinoma (RCC) cells were most susceptible to the growth inhibitory effects of IL-4. Experiments are in progress to determine other functions of IL-4R (e.g. regulation of HLA antigens, IL-4R, and cytokine production) on these tumor cells. In preliminary experiments, IL-4R structure and properties appear to be similar in both RCC and human B cell derived lymphoma cell line. In both cell types IL-4R appear to be internalized and recycled. Structure of IL- 4R and possibility of association of other subunit(s) to IL-4R is being explored by cross linking and immunoprecipitation experiments using anti- IL-4R antibodies. B. IL-4R directed targeting of a Pseudomonas exotoxin. The IL-4R expressed on human tumor cells were targeted with a chimeric protein comprised of IL-4 and PE. This protein was highly cytotoxic to IL-4R positive tumor cells, however, normal cells e.g. peripheral blood lymphocytes, endothelial cells and fibroblasts were somewhat resistant to the cytotoxic effect of IL4-PE. Studies are underway to examine anti- tumor properties of this chimeric protein against a variety of human cancers.