GENERATION OF CATALYTIC ANTIBODIES TO NEUTRALIZE COCAINE

产生中和可卡因的催化抗体

• 批准号: 2536538
• 负责人: JAN TRNOVSKY
• 金额: $ 10万
• 依托单位: ONE CELL SYSTEMS, INC
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2536538
• 关键词: B lymphocyte; abzyme; clone cells; cocaine; drug design /synthesis /production; enzyme activity; esterase; flow cytometry; hybridomas; hydrolysis; immunological substance; laboratory mouse; microcapsule; neutralizing antibody

Drug addiction and abuse exacts a heavy toll on society, the health care system, and the economy. A therapy that allows the rapid, effective neutralization of addictive drugs in vivo would enjoy extensive use. Studies in the 1970's showed that conventional antibodies could block heroin's effects in addicted monkeys, but these antibodies had slow kinetics and were effective only with low doses of the addictive substance. However, some catalytic antibodies have exhibited kinetics similar to naturally occurring enzymes and, therefore, could prove effective in treating drug addiction. In the proposed research studies, research collaborators at The Scripps Research Institute will generate antibodies that selectively degrade cocaine via ester hydrolysis. Then hybridomas secreting these antibodies will be identified and isolated using One Cell Systems' proprietary gel microdrop (GMD) secretion assay combined with fluorescent activated cell sorting (FACS). The GMD technology is ideally suited to isolating rare hybridomas that are expected to produce relatively small amounts of the desired catalytic antibodies. Development of pharmacotherapies for substances of abuse are urgently needed. PROPOSED COMMERCIAL APPLICATION: Isolation of cocaine specific catalytic antibodies for systemic in vivo administration would have significant therapeutic utility. The novel assay and recovery method is expected to have wide utility for discovery of a variety of catalytic antibodies for therapeutic as well as industrial use.

吸毒成瘾和虐待给社会带来了沉重的损失，医疗保健 系统和经济。一种允许快速有效的疗法 体内中和吸毒药物的中和会广泛使用。 1970年代的研究表明，常规抗体可能会阻塞 海洛因在上瘾的猴子中的作用，但是这些抗体缓慢 动力学，只有低剂量的上瘾有效 物质。但是，一些催化抗体表现出动力学 类似于天然发生的酶，因此可以证明 有效治疗吸毒成瘾。在拟议的研究中， Scripps研究所的研究合作者将产生 通过酯水解选择性降解可卡因的抗体。 然后 分泌这些抗体的杂交瘤将被鉴定并隔离 使用一个细胞系统的专有凝胶微旋转（GMD）分泌分析 结合荧光活化的细胞分选（FACS）。 GMD 技术非常适合隔离稀有杂交瘤 预计会产生相对少量的所需催化 抗体。开发用于滥用物质的药物治疗是 迫切需要。 拟议的商业应用： 全身体内可卡因特异性催化抗体的分离 管理将具有明显的治疗效用。小说测定法 预计恢复方法将具有广泛的实用程序来发现 用于治疗和工业用途的各种催化抗体。