Study of gamma interferon agonists/mimetics

描述（由申请方提供）：γ干扰素（IFN γ）是一种重要的细胞因子，用于介导健康所必需的功能，特别是通过CD 4 T辅助1（Th 1）细胞介导或维持的功能。此外，IFN γ具有直接的抗病毒和抗细胞（抗肿瘤）活性。因此，IFN γ模拟物的开发对于感染性疾病和癌症的免疫治疗具有重要意义。下面列出的具体目的直接测试了此类模拟物的合理开发以及它们在介导IFN γ活性中的用途。 1.基于与生物活性IFN γ C-末端肽的序列和结构相似性合成IFN γ肽模拟物。 2.比较几种细胞内递送IFN γ肽的方法，包括化学修饰和分子表达系统的使用。 3.确定IFN γ肽模拟物在癌细胞中JAK/STAT激活、肿瘤抑制基因p21 WAF/CIP上调和neu/HER-2原癌基因下调方面的信号传导功能。 4.确定IFN的细胞功能？肽模拟物的抗病毒活性、抗细胞（抗肿瘤）活性和MHC II类分子的上调。 5.确定IFN γ模拟肽在病毒感染和癌症的小鼠模型中的生物活性。

DESCRIPTION (provided by applicant): Gamma interferon (IFNgamma) is an essential cytokine for mediation of functions that are obligatory for good health, particularly that mediated through or maintained through CD4 T helper1 (Th1) cells. Further, IFNgamma possesses direct antiviral and anticellular (antitumor) activity. Thus, the development of IFNgamma mimetics has important implications for immune therapy in infectious diseases and cancer. The Specific Aims listed below directly test both the rational development of such mimetics as well as their use in the mediation of IFNgamma activity. 1. Synthesis of IFNgamma peptide mimetics based on sequence and structural similarity to biologically active IFNgamma C-terminal peptides. 2. Compare several methods for delivery of IFNgamma peptides intracellularly, including chemical modification and use of molecular expression systems. 3. Determine signaling function of IFNgamma peptide mimetics in terms of JAK/STAT activation, upregulation of tumor suppressor gene p21WAF/CIP, and down regulation of neu/HER-2protooncogene in cancer cells. 4. Determine cellular function of IFN? peptide mimetics in terms of antiviral activity, anticellular (antitumor) activity, and upregulation of MHC class II molecules. 5. Determine biological activity of IFNgamma mimetic peptides in mouse models of virus infection and cancer.