GNETIC IMMUNOTHERAPY IN HIV 1 POSITIVE PATIENTS

直接接种dna已被证明可以诱导广泛的 对HIV-1的免疫反应，包括体液免疫， 特异性辅助性细胞应答和特异性CTL 回应。我们的假设是间歇性的艾滋病毒 对受损免疫的抗原特异性刺激 该系统将使艾滋病毒感染患者部分受益 恢复免疫能力。我们打算刺激 人类免疫缺陷病毒感染者的免疫应答 多次肌肉注射病毒 蛋白质产生dna质粒(S)。 总共计划进行4项临床试验，从 第一阶段试验，主要是为了调查 肌肉内DNA质粒法的安全性和安全性 在几个剂量水平下的单个质粒组 无症状的艾滋病毒感染者(试验1、试验2 #3)。使用HIV-1 Gag/pol质粒的第一次试验将 在安全性和可能的免疫原性被 建立在SIV模型中，但目标是开始这一点 在该计划的第一年内进行试用。第二个和 第三项研究将紧随其后，基本上是相同的 将设计作为第一次试验，并根据需要进行修改 解决出现的安全或免疫原性问题。这个 研究计划已被设计为向前推进，缩小范围 调查的重点是允许可管理的试验规模和 对2个社会变革管理计划第一阶段/第二阶段研究的有效评价 最多2个有希望的质粒或质粒组合 由较早阶段I确定的有效剂量 审判。到资助期结束时，艾滋病毒患者- 相关疾病将有权获得这些实验 4号试验背景下的治疗。 拟议研究的长期目标是推动这一点 有希望的新治疗方法进入和通过初步 I期临床试验并进入初步疗效 用最有希望的质粒(S)进行的I/II期试验 4年授权期结束。

Direct DNA inoculation has been shown to induce broad immune responses against HIV-1, including humoral immunity, specific helper cell responses as well as specific CTL responses. It is our hypothesis that intermittent HIV antigen-specific stimulation of the compromised immune system will benefit the HIV infected patient by partially reconsitituting immune competence. We intend to stimulate the immune response in HIV-infected patients by administering multiple intramuscular injections of viral protein-producing DNA plaslmid(s). A total of 4 clinical trials are planned, beginning with phase I trials which are primarily intended to investigate the safety of the intramuscular DNA plasmid technique and of the individual plasmids at several dose levels in asymptomatic, HIV-infected individuals (Trials #1, #2 land #3). The first trial using the HIV-1 gag/pol plasmid will be initiated after safety and possibly immunogenicity are established in the SIV model but the goal is to start this trial within the first year of the program. The second and third studies will follow and will be essentially the same design as the first trial with modifications as needed to address safety or immunogenicity issues that arise. The research plan has been designed to move forward, narrowing the investigative focus to allow manageable trial sizes and efficient evaluations into phase I/II study of the 2 most promising plasmids or plasmid combinations at the 2 most effective doses as determined by the earlier phase I trials. By the end of the grant period, patients with HIV- related disease will have access to these experimental therapies in the context of Trial #4. The long-term goal of the proposed research is to move this promising new therapeutic approach into and through initial phase I clinical trials and to enter preliminary efficacy phase I/II trials with the most promising plasmid(s) by the end of the 4-year grant period.