MODULATION OF THE ANTITUMOR EFFECT OF INTERFERON

干扰素（IFN-α，IFN-β和IFN-γ）是天然的 具有抗病毒、免疫调节和 抗增殖活性。 一些临床试验 研究了干扰素的临床潜力。 不幸的是， 虽然他们表现出真实的承诺， 癌症类型，它们的有效性有限， 还没有发现对大多数类型都有很强的效力， 癌症检测 此外，干扰素疗法具有许多缺点。 副作用包括骨髓抑制 一个主要 挑战在于增加干扰素的抗肿瘤活性 同时减少或缓和它们的副作用。 这项建议 通过1）评估联合干扰素 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 活性; 2）评估集落刺激的组合效应 因子和其他骨髓调节剂， 使干扰素的骨髓抑制作用最小化 治疗; 3）从IFN-γ中去除干扰素作用的抑制剂， γ制剂作为最大化IFN-γ的手段 活性;和，4）评价抗肿瘤的联合作用 药物和干扰素作为一种手段，最大限度地提高其抗肿瘤 活动 该研究旨在研究基础 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.