PASSIVE IMMUNITY TO COCAINE USING NOVEL HUMAN ANTIBODIES

描述：(申请人摘要) 我们计划利用一种独特的专有转基因小鼠系 生产人免疫球蛋白以产生人的单抗 抗可卡因抗体。这些人类抗体应该被证明适合于 可卡因依赖患者的被动免疫治疗 对可卡因成瘾的有效治疗。人源单抗的应用 抗可卡因抗体应该否定物种的问题 到目前为止，不相容限制了被动的使用 免疫疗法。积极参与开发和开发的调查人员 作为我们NIDA赞助的可卡因药物治疗的一部分进行评估 药物开发研究单位正在与一组 学术和行业调查人员积极开发小说 免疫治疗技术。这项SPIRCAP提案的总体目标是： 1)在转基因小鼠中产生抗可卡因的人免疫球蛋白G 回应。然后制备、鉴定和分离脾细胞--小鼠骨髓瘤 分泌人抗可卡因单抗的杂交瘤。 2)根据纯化的抗体的亲和力和 可卡因与可卡因代谢产物结合的特异性 相关化合物。3)确定选定的人类抗可卡因的效果 抗体对小鼠行为学和药代动力学的影响 在老鼠身上注射可卡因，并选择最适合晋升的候选人。4)扩容 抗美国食品和药物管理局要求纯度的可卡因单抗的制备 用于动物毒性研究的足够数量的标准，然后 第一阶段人体安全试验。5)评估具有特征性的 GLP设施中的抗可卡因抗体以及文件和IND应用程序 FDA将进入第一阶段临床试验。6)确定任何毒性 并测量抗体在人体内的药代动力学。的成功之处 这一SPIRCAP计划将由人类抗病毒能力来定义 可卡因抗体安全地改变可卡因和可卡因的药代动力学 显著降低脑脊液中可卡因浓度。这些研究将 构成向FDA提出申请的基础 人源性抗可卡因单抗II期临床鉴定 确定可卡因被动免疫疗法疗效的试验 虐待。

DESCRIPTION: (Applicant's Abstract) We plan to utilize a unique proprietary transgenic mouse line engineered to produce human immunoglobulins in order to generate human monoclonal anti-cocaine antibodies. These human antibodies should prove suitable for passive immunotherapy of cocaine dependent patients resulting in an effective treatment for cocaine addiction. The use of human monoclonal anti-cocaine antibodies should negate the problem of species incompatibility which has to date restricted the use of passive immunotherapy. Investigators actively working on the development and assessment of cocaine pharmacotherapy as part of our NIDA sponsored Medication Development Research Unit are collaborating with a group of academic and industrial investigators actively developing novel immunotherapy techniques. The overall goals of this SPIRCAP proposal are: 1) Generate in the transgenic mice an anti-cocaine human IgG immune response. Then produce, identify and isolate spleen cell-mouse myeloma hybridomas secreting individual human anti-cocaine monoclonal antibodies. 2) Characterize the purified antibodies with respect to their affinity and specificity for cocaine binding relative to cocaine metabolites and related compounds. 3) Determine the effects of selected human anti-cocaine antibodies on the behavioral effects and on the pharmacokinetics of cocaine in rats and select the best candidate for advancement. 4) Scale-up production of the anti-cocaine monoclonal antibody to FDA-required purity standards in sufficient quantities for animal toxicity studies and then phase 1 human safety trials. 5) Assess animal toxicity of a characterized anti-cocaine antibody in a GLP facility and file and IND application with the FDA to proceed into phase 1 clinical trials. 6) Determine any toxicity and measure the pharmacokinetics of the antibody in humans. The success of this SPIRCAP program will be defined by the ability of a human anti- cocaine antibody to safely modify the pharmacokinetics of cocaine and significantly decrease CSF concentrations of cocaine. These studies will form the basis for an application to the FDA for advancement of an identified human monoclonal anti-cocaine antibody to Phase II clinical trials to determine the efficacy of a passive immunotherapy of cocaine abuse.