ADC IMMUNOTHERAPY USING REPLICONS WHICH ENCODE CYTOKINES

描述：开发有效的输送系统， 中枢神经系统的治疗对艾滋病痴呆患者至关重要 复杂相关功能障碍。 ADC的实际治疗可能更多 有效的，如果在CNS内本地颁布，以避免问题 与全身暴露于生物活性治疗剂有关。 衣壳化 复制子被认为符合这些标准，因为它们具有 通过血脑屏障的固有能力， 局部和非侵入性递送至CNS。 这方面的研究 这项提案将研究复制子在不同细胞中传播的药代动力学。 小鼠和大鼠的BBB。 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 CNS内的细胞因子。 拟议的实验将评估 直接从小鼠的CNS组织表达TGFB，并且还将测量 TGFB的生物活性通过分析已知的特异性基因的诱导， 对TGFB作出回应。第二阶段的研究将把这项技术应用于一个 ADC的SCID小鼠模型，通过测试 编码TGFB或其它免疫抑制细胞因子的复制子。 拟议商业应用：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