title: Development of murine monoclonal antibodies to methamphetamine and methamphetamine analogues.
abstract: Methamphetamine and ecstasy are addictive drugs that cause major health problems in young people. Here we report on the development of high-affinity monoclonal antibodies to methamphetamine and its analogues, which may constitute powerful tools for antibody-based therapy. Six haptens, methamphetamine and ecstasy analogues, were synthesized, linked to a carrier protein and injected into mice. Several specific monoclonal antibodies were subsequently obtained following fusion of splenocytes from the immunized animals, with Sp2/O cells. Antibody specificity was fully investigated by competition ELISA, using a series of analogues, to identify specific amphetamine and/or ecstasy-specific antibodies. Antibody affinity was estimated to be in the range of 10(8) M(-1) with an enantiomeric hapten. Finally, two characteristic hybridoma clones (DAS-M243-6H5 and DAS-M278-4B12), secreting specific and potent mAbs were isolated. The development of drug-specific antibodies as in this study may provide promising therapeutic insight into how to neutralize methamphetamine in vivo during acute intoxication.
authors.affiliation: Etablissement Français du Sang, Laboratoire de Biotechnologie, 34 bd J Monnet, BP 91115, 44011 Nantes cedex 01, France.
authors.forename: Yannic
authors.initials: Y
authors.lastname: Danger
authors.forename: Caroline
authors.initials: C
authors.lastname: Gadjou
authors.forename: Anne
authors.initials: A
authors.lastname: Devys
authors.forename: Hervé
authors.initials: H
authors.lastname: Galons
authors.forename: Dominique
authors.initials: D
authors.lastname: Blanchard
authors.forename: Gilles
authors.initials: G
authors.lastname: Folléa
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000302:isolation & purification / Q000627:therapeutic use; D000915:Antibody Affinity; D000918:Antibody Specificity; D006241:Haptens / Q000737:chemistry; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D013287:Illicit Drugs / Q000276:immunology / Q000633:toxicity; D007167:Immunotherapy; D066298:In Vitro Techniques; D008694:Methamphetamine / Q000031:analogs & derivatives / Q000276:immunology* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000276:immunology / Q000633:toxicity; D019966:Substance-Related Disorders / Q000628:therapy
chemical_list: D000911:Antibodies, Monoclonal; D006241:Haptens; D013287:Illicit Drugs; D008694:Methamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine