Copolymers for suppression of autoimmune diseases, and methods of use

摘要

Random three- and four-amino acid copolymers having lengths of 14-, 35- and 50-amino acid residues are provided. Fifty-mers of FEAK were effective inhibitors of MBP 85-99- or proteolipid protein (PLP) 40-60-specific HLA-DR-2-restricted T cell clones. These copolymers efficiently suppressed the mouse disease EAE, which was induced in a susceptible SJL/J (H-2s) strain of mice with either whole spinal cord homogenate (WSCH) or with the encephalitogenic epitope PLP 139-151 (SEQ ID NO:4). YFAK 50-mer having a molar ratio of about Y 0.8:F 0.2 inhibited binding of biotinylated MBP 85-99 epitope to HLA-DR-2 molecules more efficiently than either unlabeled MBP 85-99 or Copaxone®. YFAK and FAK copolymers efficiently suppressed EAE induced in SJL/J (H-2S) mice with the encephalitogenic epitope PLP 139-151. Copolymers YFAK, VYAK and tryptophan-containing VWAK were efficacious in alleviating severity and duration of symptoms of EAE induced by MBP 85-99 (SEQ ID NO:2), in a humanized mouse model expressing genes for both an HLA-DR-2 linked to multiple sclerosis (MS) in humans and for a T cell receptor from an MS patient.