Rheumatoid Arthritis is a chronic inflammatory disease that mainly targets the synovial membrane, cartilage and bone. It affects about 1% of the global population and is associated with significant morbidity and increased mortality. Non-steroidal, as well as steroidal anti-inflammatory medicines and now more commonly the use of anti-TNFα related therapies are the current standard treatment of patients with advanced RA, but information suggests that over half of the RA patients treated do not respond to current anti-TNFα drugs such as etanercept (Enbrel®) and infliximab (Remicade®).
New preclinical data presented by CEL-SCI demonstrated that its investigational new drug candidate CEL-4000 has the potential for use as a therapeutic vaccine to treat rheumatoid arthritis. CEL-4000 has been developed using CEL-SCI’s patented LEAPS (Ligand Epitope Antigen Presentation System) technology. Data were presented by Daniel Zimmerman, Ph.D., CEL-SCI’s Senior Vice President of Research, Cellular Immunology, at the American College of Rheumatology’s Annual Meeting in Washington DC. The poster presentation titled, “A Therapeutic Peptide Vaccine Reduces Pro-inflammatory Responses and Suppresses Arthritis in the Cartilage Proteoglycan G1 Domain-induced Mouse Model of Rheumatoid Arthritis,” was presented earlier this month.
This study was supported in part by funding of a Phase I Small Business Innovation Research (SBIR) grant in the amount of $225,000 from the National Institute of Arthritis Muscoskeletal and Skin Diseases (NIAMS), a part of the National Institutes of Health (NIH). The study was conducted in collaboration with Drs. Katalin Mikecz and Tibor Glant, and their research team at Rush University Medical Center in Chicago, IL.
“These findings, in conjunction with the results from earlier animal studies with LEAPS vaccines, support the potential that LEAPS vaccines may be useful as a therapeutic treatment for different types of rheumatoid arthritis. LEAPS vaccines may be advantageous to other therapies because they appear to act early on the immune system and inhibit the production of disease-promoting inflammatory cytokines. This is a significant step forward in the development of the LEAPS technology,” said Dr. Zimmerman.
This efficacy study evaluated the LEAPS vaccine’s effect in both the Proteoglycan (PG) induced arthritis (PGIA) and the closely related recombinant huG1 domain of PG (GIA) both in animal models of rheumatoid arthritis (RA) having a dominant T helper 1 (Th1) cytokine profile. These animal models were developed and have been studied extensively in Dr. Glant’s laboratory for over 25 years and are closely related to the human condition of many RA patients. The PGIA and GIA model also exhibits rheumatoid factor (Rf), RA-specific antibodies ACPA (anti citrulline peptide antibodies) and tend to develop spondylitis not usually seen in other RA models.
Disease severity, as determined based on the Arthritis Index and histopathology, was suppressed in mice treated with the LEAPS vaccine when compared to controls. As initially reported based on preliminary data in the PGIA model only, the reduction in disease (RA) severity following LEAPS vaccination with CEL-4000 (DerG-PG70 treatment) correlated with up-regulation of T regulatory cells (Treg) and Th2 cytokines (IL-10, IL-4 and TGF-β), reduced proliferation of PG specific T lymphocytes, and decreases in the production of Th1 and Th17 cytokines (IFN-γ and IL-17).