title: The T cell-selective IL-2 mutant AIC284 mediates protection in a rat model of Multiple Sclerosis.
abstract: Targeting regulatory T cells (Treg cells) with interleukin-2 (IL-2) constitutes a novel therapeutic approach for autoimmunity. As anti-cancer therapy with IL-2 has revealed substantial toxicities a mutated human IL-2 molecule, termed AIC284 (formerly BAY 50-4798), has been developed to reduce these side effects. To assess whether AIC284 is efficacious in autoimmunity, we studied its therapeutic potential in an animal model for Multiple Sclerosis. Treatment of Lewis rats with AIC284 increased Treg cell numbers and protected the rats from Experimental Autoimmune Encephalomyelitis (EAE). AIC284 might, thus, also efficiently prevent progression of autoimmune diseases in humans.
authors.affiliation: University Hospital Würzburg, Department of Neurology, Josef-Schneider-Strasse 11, D-97080 Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Weishaupt
authors.affiliation: AiCuris GmbH & Co. KG, Friedrich-Ebert-Str. 475, Building 302, D-42117 Wuppertal, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Paulsen
authors.affiliation: University of Würzburg, Institute for Virology and Immunobiology, Versbacher Str. 7, D-97078 Würzburg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Werner
authors.affiliation: University of Würzburg, Institute for Virology and Immunobiology, Versbacher Str. 7, D-97078 Würzburg, Germany.
authors.forename: Nelli
authors.initials: N
authors.lastname: Wolf
authors.affiliation: University Hospital Würzburg, Department of Neurology, Josef-Schneider-Strasse 11, D-97080 Würzburg, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Köllner
authors.affiliation: AiCuris GmbH & Co. KG, Friedrich-Ebert-Str. 475, Building 302, D-42117 Wuppertal, Germany.
authors.forename: Helga
authors.initials: H
authors.lastname: Rübsamen-Schaeff
authors.affiliation: University of Würzburg, Institute for Virology and Immunobiology, Versbacher Str. 7, D-97078 Würzburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hünig
authors.affiliation: University of Würzburg, Institute for Virology and Immunobiology, Versbacher Str. 7, D-97078 Würzburg, Germany. Electronic address: kerkau@mail.uni-wuerzburg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kerkau
authors.affiliation: University of Würzburg, Institute for Virology and Immunobiology, Versbacher Str. 7, D-97078 Würzburg, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Beyersdorf
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015551:Autoimmunity / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D007376:Interleukin-2 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000187:drug effects; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D011654:Pulmonary Edema / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
chemical_list: D017304:Annexin A5; D015703:Antigens, CD; D000970:Antineoplastic Agents; D007376:Interleukin-2; D011994:Recombinant Proteins; C082598:aldesleukin
keywords: AIC284; EAE; Immunotherapy; Lewis rat; Regulatory T cells