CLINICAL TRIALS OF BIOLOGICAL RESPONSE MODIFIERS

生物反应调节剂的临床试验

• 批准号: 2443332
• 负责人: MICHAEL T LOTZE
• 金额: $ 56.87万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-16 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2443332
• 关键词: aminoguanidine; biological response modifiers; clinical research; clinical trial phase I; combination chemotherapy; cytokine; drug interactions; human subject; human therapy evaluation; interferon alpha; melanoma; monoclonal antibody; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; pentoxifylline; retinoate; suramin

We will conduct clinical trials with a large number of different Biologic Response Modifiers including combinations of agents and approaches. Given our expertise we believe that we are in a particularly good position to conduct Phase I trials of BRM's and have the broad and well established scientific base to appropriately generate and test scientific hypotheses and explore mechanisms of action of current biologic agents. We are in position to test the following: (1) approaches which utilize or modify immunologic mechanism: we have ongoing preclinical and clinical programs encompassing a range of agents and approaches including cytokines, (IL-2, IL-4, IL-7, IL-10 and IL-12), agents modifying the toxicity of cytokines (preclinical studies of NO synthase inhibitors such as amino guanidine, TNF inhibitors such as pentoxifylline), adoptive immunotherapies using antibodies (R24, Bec2) or cellular reagents (TIL, ANK), and cytokine gene therapies (IL-4); (2) approaches using naturally occurring or recombinantly produced regulatory molecules (ongoing clinical protocols of alpha interferon and transretinoic acid (TRA), preclinical studies of antisense molecules directed at fibroblast growth factor for the treatment of melanoma as well as monoclonal antibodies and related constructs (completed clinical trials of RF24 and proposed studies of the anti-idiotypic antibody, Bec-2), and (3) active clinical and preclinical programs in testing differentiation agents such as interferon, TRA and Suramin. (4) More approaches utilizing T-cell defined tumor epitopes in constructing tumor vaccine.

我们将使用大量不同的生物制剂进行临床试验， 反应调节剂，包括药剂和方法的组合。 鉴于我们的专业知识，我们相信，我们在一个特别好的 位置进行BRM的第一阶段试验，并具有广泛和良好的 建立科学基础，以适当生成和测试科学 假设和探索当前生物制剂的作用机制。 我们可以测试以下内容：（1）利用 或改变免疫机制：我们正在进行临床前和 临床项目包括一系列药物和方法，包括 细胞因子（IL-2、IL-4、IL-7、IL-10和IL-12），修饰细胞因子的试剂， 细胞因子的毒性（NO合酶抑制剂的临床前研究， 如氨基胍，TNF抑制剂如戊茶碱），过继性 使用抗体（R24，Bec 2）或细胞试剂（TIL， ANK）和细胞因子基因疗法（IL-4）;（2）使用天然 发生或重组产生的调节分子（正在进行 α干扰素和反式视黄酸（TRA）的临床方案， 针对成纤维细胞生长的反义分子的临床前研究 用于治疗黑色素瘤的因子以及单克隆抗体， 相关构建体（已完成的RF 24临床试验和建议的 抗独特型抗体Bec-2的研究），和（3）活性临床 和临床前项目，用于测试分化剂， 干扰素TRA和苏拉明 (4)更多利用T细胞的方法 确定的肿瘤表位构建肿瘤疫苗。