MODULATION OF THE ANTITUMOR EFFECT OF INTERFERON

干扰素(干扰素-α、干扰素-β和干扰素-γ)是天然的 宿主蛋白具有抗病毒、免疫调节和 抗增殖活性。一些临床试验已经 检查干扰素的临床潜力。不幸的是， 虽然他们表现出了真正的希望来控制某些 癌症的类型，它们的有效性和 尚未发现对大多数类型的病毒有很强的抵抗力 检测出的癌症。此外，干扰素疗法有许多 副作用，包括骨髓抑制。一位少校 挑战是增加干扰素的抗肿瘤活性 同时减少或减轻它们的副作用。这项建议 通过1)评估联合干扰素来关注这一挑战 治疗(干扰素-γ加干扰素-α或干扰素-β) 作为最大化干扰素的手段的各种治疗方案 活性；2)评价菌落刺激的综合效果 因子和其他骨髓调节剂作为一种手段 尽量减少干扰素的骨髓抑制作用 治疗；3)从干扰素中去除干扰素作用的抑制物- 作为使干扰素-γ最大化的手段的伽马制剂 活性；以及，4)评估抗肿瘤的联合作用 药物和干扰素作为最大化其抗肿瘤作用的手段 活动。这项拟议的研究旨在调查基本的 机制，同时为临床提供重要的见解 干扰素的应用。

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.