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A human recombinant monoclonal antibody to cocaine: Preparation,characterization and behavioral studies
Affiliation:1. Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA;2. 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;3. Committee on Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA;4. Worm Institute of Medical Research (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA;1. School of Studies in Chemistry, Pt. Ravishankar Shukla University, Raipur (C.G.) 492010, India;2. Department of Chemistry and Biochemistry, Faculty of Medicine, University of Zargreb, Šalata 3, 10000 Zagreb, Croatia;3. University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, Hradec Kralove, Czech Republic;4. University Hospital, Biomedical Research Center, Sokolska 581, 50005 Hradec Kralove, Czech Republic;5. Process Technology Development Division, Defence Research & Development Establishment, Jhansi Road, Gwalior 474002, India;1. Friedrich-Alexander University of Erlangen-Nürnberg, Department of Chemistry and Pharmacy, Organic Chemistry II, Henkestr. 42, 91054 Erlangen, Germany;2. Ruprecht-Karls University of Heidelberg, Institute of Inorganic Chemistry, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany;3. Ruprecht-Karls University of Heidelberg, BioQuant, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany;1. College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea;2. College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea
Abstract: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.
Keywords:Cocaine  Overdose  Immunopharmacotherapy  Passive immunization  Monoclonal antibody
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