Nature Medicine
2, 1129 - 1132 (1996)
doi:10.1038/nm1096-1129
Efficacy of a therapeutic cocaine vaccine in rodent modelsBarbara S. Fox1, Kathleen M. Kantak2, Melissa A. Edwards2, Kerry M. Black1, Brenda K. Bollinger1, Alison J. Botka1, Tammy L. French1, Terry L. Thompson1, Victoria C. Schad1, 3, Julia L. Greenstein1, 3, Malcolm L. Gefter1, Mark A. Exley1, Philip A. Swain1
& Thomas J. Briner1
1ImmuLogic Pharmaceutical Corporation, 610 Lincoln Street, Waltham, Massachusetts 02154, USA
2Department of Psychology, 64 Cummington Street, Boston University, Boston, Massachusetts 02215, USA
3V.C.S. and J.L.G. present address: BioTransplant, Inc., Building 75,Third Avenue, Charlestown Navy Yard, Charlestown, Massachusetts 02129, USA Cocaine abuse is a major medical and public health concern in the United States, with approximately 2.1 million people dependent on cocaine1. Pharmacological approaches to the treatment of cocaine addiction have thus far been disappointing2,3, and new therapies are urgently needed. This paper describes an immunological approach to cocaine addiction. Antibody therapy for neutralization of abused drugs has been described previously4, including a recent paper demonstrating the induction of anti−cocaine antibodies5. However, both the rapidity of entry of cocaine into the brain6 and the high doses of cocaine frequently encountered7 have created challenges for an antibody−based therapy. Here we demonstrate that antibodies are efficacious in an animal model of addiction. Intravenous cocaine self−administration in rats was inhibited by passive transfer of an anti−cocaine monoclonal antibody. To actively induce anti−cocaine antibodies, a cocaine vaccine was developed that generated a high−titer, long−lasting antibody response in mice. Immunized mice displayed a significant change in cocaine pharmacokinetics, with decreased levels of cocaine measured in the brain of immunized mice only 30 seconds after intravenous (i.v.) administration of cocaine. These data establish the feasibility of a therapeutic cocaine vaccine for the treatment of cocaine addiction.
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