CEL-2000: A therapeutic vaccine for rheumatoid arthritis arrests disease development and alters serum cytokine/chemokine patterns in the bovine collagen type II induced arthritis in the DBA mouse model

CEL-2000: A therapeutic vaccine for rheumatoid arthritis arrests disease development and alters serum cytokine/chemokine patterns in the bovine collagen type II induced arthritis in the DBA mouse model

Zimmerman D H; Taylor P; Bendele A; Carambula R; Duzant Y; Lowe V; O'Neill S P; Talor E; Rosenthal K S

International Immunopharmacology

2010

2010-04

The mouse model of collagen induced arthritis (CIA) effectively mimics human disease and thus is useful for testing and development of rheumatoid arthritis (RA) therapies. We developed a Ligand Epitope Antigen Presentation System (LEAPS) peptide hetero-conjugate vaccine containing an epitope of human collagen type II (CEL-2000) that acted as a therapeutic vaccine in the collagen induced arthritis (CIA) mouse model. LEAPS technology converts a small peptide containing a disease specific epitope into an immunogen by attaching it to an immune or T cell binding peptide (I/TCBL). For CEL-2000, a peptide from human collagen type II (254-273) is attached to the I/TCBL peptide from human in microglobulin (J). Treatment with CEL-2000 limited disease (CIA) progression, as demonstrated by reduced Arthritic Index (AI) score, and footpad swelling. Efficacy was confirmed by histopathological microscopic examination of tissues at the end of the study. CEL-2000 limited disease progression as well or better than the etanercept (Enbrel) therapeutic control with significantly better histopathological results than the etanercept treated mice. Most interestingly, CEL-2000 therapy modulated serum cytokine levels with an increase in IL-12p70 and IL-10, which are not seen with etanercept therapy, and reduced IL-17 and INF-alpha, also seen with etanercept, among other cytokines studied. CEL-2000 was safe and well tolerated for the mice that received 5 injections given every 2 weeks in a 90 day study supporting its potential usage for long term therapy. These studies demonstrate that fewer treatments with CEL-2000 provide therapy at least as effective as etanercept by specifically modulating the disease producing autoimmune response. (C) 2010 Elsevier B.V. All rights reserved.

acellular pertussis-vaccine; auto-immune; beta-chain; binding-site; Collagen induced arthritis; identification; immune responses; immunogenicity; Immunology; inflammation; peptide analog; Pharmacology & Pharmacy; Regulation of cytokines in autoimmunity; regulatory t-cells; rheumatoid-arthritis; Therapeutic vaccine; transgenic mice; Vaccines for autoimmunity

Journal Article

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