title: 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.
abstract: 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 beta2 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 TNF-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 2weeks in a 90day 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.
authors.affiliation: Research and Development, CEL-SCI Corporation, 8229 Suite 802 Vienna, VA 22182, United States. dzimmerman@cel-sci.com
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Zimmerman
authors.forename: Patricia
authors.initials: P
authors.lastname: Taylor
authors.forename: Alison
authors.initials: A
authors.lastname: Bendele
authors.forename: Roy
authors.initials: R
authors.lastname: Carambula
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Duzant
authors.forename: Valeria
authors.initials: V
authors.lastname: Lowe
authors.forename: Sean P
authors.initials: SP
authors.lastname: O'Neill
authors.forename: Eyal
authors.initials: E
authors.lastname: Talor
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Rosenthal
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000473:pathology / Q000628:therapy*; D018925:Chemokines / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D024043:Collagen Type II; D016207:Cytokines / Q000097:blood*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D000068800:Etanercept; D005528:Foot / Q000473:pathology; D007074:Immunoglobulin G / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014612:Vaccines / Q000627:therapeutic use*; D022223:Vaccines, Subunit / Q000627:therapeutic use*
chemical_list: D018501:Antirheumatic Agents; C550459:CEL 2000; D018925:Chemokines; D024043:Collagen Type II; D016207:Cytokines; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D014612:Vaccines; D022223:Vaccines, Subunit; D000068800:Etanercept