title: Anti-interleukin-2 receptor monoclonal antibody therapy induces anti-idiotypic antibodies in mice that block both in vitro and in vivo activity.
abstract: Monoclonal antibodies (Mab) targeting certain T cell-surface proteins including the interleukin-2 (IL2) receptor molecule exert powerful immunosuppressive effects. A potential limiting factor to Mab therapy is the formation of neutralizing anti-idiotypic antibodies (Anti-Id). In this study, we demonstrate that an anti-IL2 receptor Mab, M7/20, when administered at doses which are immunosuppressive in vivo rapidly elicits an anti-idiotypic (anti-Id) antibody response. The induced antibodies are capable of blocking M7/20 binding to its target, the IL2 receptor, in vitro. Such anti-Id when given in concert with M7/20 block the expected in vivo inhibitory effects in delayed type hypersensitivity. Thus, mice respond to therapeutic doses of Mab therapy with the formation of neutralizing anti-Id. As this response is similar to that observed in humans given xenogeneic Mab, this model may be useful to further our understanding of this form of therapy.
authors.affiliation: Charles A. Dana Research Institute, Beth Israel Hospital, Boston, MA.
authors.forename: O G
authors.initials: OG
authors.lastname: Pankewycz
authors.forename: R
authors.initials: R
authors.lastname: Hassarjian
authors.forename: C
authors.initials: C
authors.lastname: Chang
authors.forename: T B
authors.initials: TB
authors.lastname: Strom
authors.forename: V E
authors.initials: VE
authors.lastname: Kelley
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002846:Chromatography, Affinity; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D006968:Hypersensitivity, Delayed; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007075:Immunoglobulin M / Q000032:analysis; D007165:Immunosuppression Therapy; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D015375:Receptors, Interleukin-2