The T cell-selective IL-2 mutant AIC284 mediates protection in a rat model of Multiple Sclerosis

J Neuroimmunol. 2015 May 15:282:63-72. doi: 10.1016/j.jneuroim.2015.03.020. Epub 2015 Mar 27.

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.

Keywords: AIC284; EAE; Immunotherapy; Lewis rat; Regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A5 / metabolism
  • Antigens, CD / metabolism
  • Antineoplastic Agents / therapeutic use*
  • Autoimmunity / drug effects
  • Cells, Cultured
  • Coculture Techniques
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Flow Cytometry
  • Interleukin-2 / analogs & derivatives*
  • Interleukin-2 / pharmacology
  • Interleukin-2 / therapeutic use
  • Killer Cells, Natural / drug effects
  • Multiple Sclerosis* / immunology
  • Multiple Sclerosis* / pathology
  • Multiple Sclerosis* / prevention & control
  • Pulmonary Edema / etiology
  • Pulmonary Edema / prevention & control
  • Rats
  • Rats, Inbred Lew
  • Recombinant Proteins / therapeutic use
  • T-Lymphocytes, Regulatory / drug effects*

Substances

  • Annexin A5
  • Antigens, CD
  • Antineoplastic Agents
  • Interleukin-2
  • Recombinant Proteins
  • aldesleukin