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MODULATION OF THE ANTITUMOR EFFECT OF INTERFERON

干扰素抗肿瘤作用的调节

基本信息

批准号：
3167329
负责人：
WILLIAM R FLEISCHMANN
金额：
$ 16.86万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-12-01 至 1990-11-30
项目状态：
已结题

项目摘要

Interferons (IFN-alpha, IFN-beta, and IFN-gamma) are natural host proteins which have antiviral, immunoregulatory, and antiproliferative activities. A number of clinical trials have examined interferons for their clinical potential. Unfortunately, while they have shown real promise for the control of certain types of cancer, they have been limited in their effectiveness and have not been found to be highly potent against most of the types of cancers tested. Further, interferon therapy has a number of side effects, including bone marrow suppression. A major challenge is to increase the antitumor activity of the interferons while reducing or moderating their side effects. This proposal focuses on this challenge by 1) evaluating combined interferon treatment (IFN-gamma plus either IFN-alpha or IFN-beta) in various treatment protocols as a means of maximizing interferon activity; 2) evaluating the combined effects of colony stimulating factors and other myeloregulatory agents as a means of minimizing the bone marrow suppressive effect of interferon therapy; 3) removing an inhibitor of interferon action from IFN- gamma preparations as a means of maximizing IFN-gamma activity; and, 4) evaluating the combined effects of antitumor drugs and interferons as a means of maximizing their antitumor activities. The proposed research seeks to investigate basic mechanisms, while providing important insights for the clinical application of interferon.

干扰素（IFN-α、IFN-β 和 IFN-γ）是天然的宿主蛋白具有抗病毒、免疫调节等作用抗增殖活性。多项临床试验已检查干扰素的临床潜力。很遗憾，虽然他们已经显示出控制某些领域的真正希望癌症类型，它们的有效性有限并且尚未发现对大多数类型具有高效作用测试的癌症。此外，干扰素疗法还具有许多副作用，包括骨髓抑制。一个专业挑战是增加干扰素的抗肿瘤活性同时减少或减轻其副作用。这个提议通过 1) 评估联合干扰素来关注这一挑战治疗（IFN-γ加IFN-α或IFN-β）作为最大化干扰素的手段的各种治疗方案活动; 2) 评估集落刺激的综合效果因素和其他骨髓调节剂作为手段最大限度地减少干扰素的骨髓抑制作用治疗; 3)从IFN-中去除干扰素作用的抑制剂 γ 制剂作为最大化 IFN-γ 的一种手段活动; 4) 评估抗肿瘤的综合效果药物和干扰素作为最大限度发挥抗肿瘤作用的手段活动。拟议的研究旨在调查基本机制，同时为临床提供重要见解干扰素的应用。