ADC IMMUNOTHERAPY USING REPLICONS WHICH ENCODE CYTOKINES

描述：开发有效的递送系统 中枢神经系统治疗对艾滋病痴呆患者至关重要 复杂相关功能障碍。对ADC的实际治疗可能会更多 如果在CNS内本地颁布，则有效，以避免问题 与全身暴露于生物活性疗法有关。已封装 复制体被建议满足这些标准，因为它们具有 固有的穿越血脑屏障的能力，这使得 对中枢神经系统的本地化和非侵入性递送。这方面的研究 该提案将研究复制子在体内的药代动力学 小鼠和大鼠的血脑屏障。进一步的研究将采用复制子载体 编码TGFb以解决复制子表达生物活性的能力 中枢神经系统内的细胞因子。拟议中的实验将评估 直接从小鼠中枢神经系统组织中表达TGFb并将检测 利用特异性基因Knowto诱导分析TGFb的生物活性 对TGFb做出回应。第二阶段研究将把这项技术应用于 通过检测SCID小鼠模型对ADC的治疗效果 编码TGFb或其他免疫抑制细胞因子的复制子。 建议的商业应用：不可用

DESCRIPTION: The development of effective delivery systems for therapeutics to the CNS is critical for AIDS patients with AIDS Dementia Complex-associated dysfunction. Practical treatments for ADC may be more effective if enacted locally within the CNS to avoid the problems associated with systemic exposure to bioactive therapeutics. Encapsidated replicons are proposed to meet these criteria, because they have an inherent capacity to traverse the blood-brain barrier, which permits localized and non-invasive delivery to the CNS. The studies in this proposal will examine the pharmacokinetics of replicon transmission across the BBB in mice and rats. Further studies will employ a replicon vector encoding TGFB to address the ability of replicons to express bioactive cytokines within the CNS. The proposed experiments will evaluate expression of TGFB directly from CNS tissue of mice and will also measure bioactivity of the TGFB by analysis of induction of specific genes know to be responsive to TGFB. Phase II studies will apply this technology to a SCID mouse model for ADC through testing of the therapeutic benefits of replicons encoding TGFB or other immunosuppressive cytokines. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE