CLINICAL TRIALS OF BIOLOGICAL RESPONSE MODIFIERS

我们将对大量不同的生物进行临床试验 响应改进剂，包括代理和方法的组合。 鉴于我们的专业知识，我们相信我们处于一个特别好的状态 能够进行BRM的第一阶段试验，并具有广泛和良好的 建立科学基础，适当地产生和测试科学 提出假说并探索当前生物制剂的作用机制。 我们已经准备好测试以下内容：(1)利用 或修改免疫机制：我们有正在进行的临床前和 包含一系列药物和方法的临床计划，包括 细胞因子(IL-2、IL-4、IL-7、IL-10和IL-12)，修饰 细胞因子的毒性(一氧化氮合酶抑制剂的临床前研究 如氨基胍、肿瘤坏死因子抑制剂，如己酮可可碱)，过继 使用抗体(R24，Bec2)或细胞试剂(TIL， ANK)和细胞因子基因疗法(IL-4)；(2)使用天然 发生的或重组产生的调节分子(正在进行 α干扰素和转维甲酸(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 治疗黑色素瘤的因子以及单抗和 相关构造(已完成的RF24临床试验和建议的 抗独特型抗体的研究(BEC-2)和(3)活跃的临床 和临床前计划，测试分化药物，如 干扰素、全反式维甲酸和苏拉明。(4)更多利用T细胞的方法 在构建肿瘤疫苗时确定肿瘤表位。

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.