Eubanks Lisa M, Ellis Beverly A, Cai Xiaoqing, Schlosburg Joel E, Janda Kim D
Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Immunology and Microbial Sciences, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Immunology and Microbial Sciences, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Committee on Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Bioorg Med Chem Lett. 2014 Oct 1;24(19):4664-4666. doi: 10.1016/j.bmcl.2014.08.035. Epub 2014 Aug 21.
Cocaine abuse remains prevalent worldwide and continues to be a major health concern; nonetheless, there is no effective therapy. Immunopharmacotherapy has emerged as a promising treatment strategy by which anti-cocaine antibodies bind to the drug blunting its effects. Previous passive immunization studies using our human monoclonal antibody, GNCgzk, resulted in protection against cocaine overdose and acute toxicity. To further realize the clinical potential of this antibody, a recombinant IgG form of the antibody has been produced in mammalian cells. This antibody displayed a high binding affinity for cocaine (low nanomolar) in line with the superior attributes of the GNCgzk antibody and reduced cocaine-induced ataxia in a cocaine overdose model.
可卡因滥用在全球范围内仍然普遍存在，并且仍然是一个主要的健康问题；尽管如此，目前尚无有效的治疗方法。免疫药物疗法已成为一种有前景的治疗策略，通过抗可卡因抗体与药物结合来减弱其作用。先前使用我们的人单克隆抗体GNCgzk进行的被动免疫研究，产生了针对可卡因过量和急性毒性的保护作用。为了进一步实现这种抗体的临床潜力，已在哺乳动物细胞中生产了该抗体的重组IgG形式。这种抗体对可卡因表现出高结合亲和力（低纳摩尔），与GNCgzk抗体的优异特性一致，并在可卡因过量模型中减轻了可卡因诱导的共济失调。
