GNETIC IMMUNOTHERAPY IN HIV 1 POSITIVE PATIENTS

直接DNA接种已显示诱导广泛的 针对HIV-1的免疫应答，包括体液免疫， 特异性辅助细胞反应以及特异性CTL 应答 我们的假设是间歇性艾滋病 免疫受损的抗原特异性刺激 该系统将使艾滋病毒感染者受益， 重建免疫能力 我们打算刺激 HIV感染者的免疫反应， 给予多次肌肉注射病毒 产生蛋白质的DNA质粒。 总共计划进行4项临床试验，首先是 I期试验主要用于研究 肌内DNA质粒技术的安全性， 在几个剂量水平下， 无症状的HIV感染者（试验1、2和 #3）。 使用HIV-1 gag/pol质粒的首次试验将 在安全性和可能的免疫原性 在SIV模型中建立，但目标是启动 在项目的第一年内进行试验。 第二和 第三项研究将随后进行，基本上是相同的 设计为首次试验，并根据需要进行修改， 解决出现的安全性或免疫原性问题。 的 研究计划已被设计向前推进，缩小 调查重点，以允许可管理的审判规模， 有效的评价纳入第I/II阶段研究的2个最 有希望的质粒或质粒组合，最多2个 早期I期试验确定的有效剂量 审判 到补助期结束时，艾滋病毒感染者- 相关疾病将有机会获得这些实验 在试验#4的背景下进行治疗。 拟议研究的长期目标是将这一点 有前途的新治疗方法， I期临床试验并进入初步疗效 I/II期试验，使用最有前途的质粒， 四年补助期结束。

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.