Direct antiproliferative effects of recombinant human interferon-alpha B/D hybrids on human tumor cell lines.
Direct antiproliferative effects of recombinant human interferon-alpha B/D hybrids on human tumor cell lines.
复制标题
重组人干扰素-α B/D 杂交体对人肿瘤细胞系的直接抗增殖作用。
作者：
I. Fidler;R. Heicappell;I. Saiki;M. Grütter;M. Horisberger;J. Nuesch
这些研究的目的是检查 16 种重组人 IFN-α B/D 杂合体针对不同组织学来源的各种人类肿瘤系的抗增殖特性，并确定是否有任何杂合分子具有免疫调节活性，可以激活正常供体外周血单核细胞的抗肿瘤特性。与NH2末端具有D结构域的杂合体相比，NH2末端具有B结构域的杂合体表现出更高的抗病毒活性和更高水平的直接抗肿瘤抗增殖活性。阳性杂交体对黑色素瘤、胶质母细胞瘤、肾癌、结肠癌和前列腺癌细胞具有直接细胞抑制作用。肿瘤细胞对IFN-α杂合体的敏感性与对IFN-γ或阿霉素的敏感性无关。正常细胞系（人胚胎成纤维细胞）的生长不受 IFN-α 杂交体的影响，但被阿霉素完全抑制。一些 IFN-α 杂交体还对小鼠黑色素瘤、肺癌和纤维肉瘤细胞系具有细胞抑制作用，尽管其水平低于对人类细胞的水平。单核细胞与 NH2 末端具有 B 结构域的 IFN-α 杂交体一起孵育也与显着的抗肿瘤细胞毒性相关。然而，动力学研究表明，这种活性归因于单核细胞上携带的 IFN-α，并直接作用于肿瘤细胞。我们得出的结论是，重组人 IFN-α B/D 杂交体对多种人类肿瘤系具有有效的直接抗增殖活性。
The purpose of these studies was to examine the antiproliferative properties of 16 recombinant human IFN-alpha B/D hybrids against various human tumor lines of different histological origin and to determine whether any of the hybrid molecules possessed immunomodulating activity that could active antitumor properties in peripheral blood monocytes of normal donors. Hybrids with the B domain at the NH2 terminal end exhibited higher activity for antiviral activity and a higher level of direct antitumor antiproliferative activities as compared with hybrids with the D domain at the NH2 terminal end. The positive hybrids were directly cytostatic to melanoma, glioblastoma, renal carcinoma, colon carcinoma, and prostatic carcinoma cells. Tumor cell sensitivity to IFN-alpha hybrids was independent of sensitivity to IFN-gamma or to Adriamycin. The growth of a normal cell line (human embryo fibroblast) was unaffected by IFN-alpha hybrids but was completely arrested by Adriamycin. Some of the IFN-alpha hybrids were also cytostatic to mouse melanoma, lung carcinoma, and fibrosarcoma cell lines, albeit at lower levels than they were to human cells. The incubation of monocytes with IFN-alpha hybrids with the B domain at the NH2 terminal end was also associated with marked antitumor cytotoxicity. Kinetic studies, however, indicated that this activity was attributable to IFN-alpha carried on monocytes and acting directly on tumor cells. We conclude that recombinant human IFN-alpha B/D hybrids possess potent direct antiproliferative activity against a large variety of human tumor lines.
干扰素：生化、细胞生长抑制和免疫作用。
DOI：
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发表时间：
1981
期刊：
Progress in hematology
影响因子：
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作者：
Borden,EC;Ball,LA
通讯作者：
Ball,LA