CEL-SCI’s rheumatoid arthritis vaccine CEL-2000 was discovered as part of work with the company’s ongoing research and development activities with its LEAPS (Ligand Epitope Antigen Presentation System) technology. LEAPS is a novel T-cell modulation platform technology that enables the company to design and synthesize proprietary immunogens.
The results were published in the scientific peer-reviewed Journal of International Immunopharmacology (online edition) in an article titled ‘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-SCI claimed that CEL-2000, administered after disease (RA) symptoms had started, prevented, in a statistically significant manner, the further advancement of arthritic conditions, including joint swelling and deformation, bone and cartilage changes and was accompanied by serum cytokine alterations over the CEL-2000 treatment period with comparable or better activity than the etanercept (Enbrel) therapy.
The mode of action is very consistent with the findings of induction of IL-12 followed by interferon gamma and an inhibition of TNF-alpha and IL-17 production. TNF-alpha and IL-17 are both major cytokines for induction of the pathology seen in rheumatoid arthritis and TNF-alpha is the aim of many current RA therapies such as Enbrel, Remicaid, and Humaria.
Enbrel is a soluble recombinant protein of a human TNF-alpha receptor linked to human IgG Fc. In some cases, human or humanized monoclonal antibodies specific against TNF-alpha have also been used for therapy in rheumatoid arthritis. These therapies remove or inactivate TNF-alpha, a natural human cytokine required in many immune functions for normal defenses.
Geert Kersten, CEO of CEL-SCI, said: “These experimental results were achieved through a reduction of the inflammatory response that is known to attack the patients’ joints. The mode of action of CEL-2000 in RA appears to be similar to our new investigational therapy for H1N1 hospitalized patients, as it attempts to avoid the excess TNF-alpha and other pro-inflammatory cytokines.
“We feel that this new data is encouraging both for this rheumatoid arthritis vaccine as well as in support of our H1N1 treatment currently under development.”
CEL-SCI said that, in these studies, mice were injected with collagen to induce the autoimmune (RA) disease. Therapy with CEL-2000 was initiated after disease (RA) symptoms have been established and treatment continued for 28 days after the initiation of a significant, uniform, and measurable level of arthritic disease in groups of mice. CEL-2000 was administered only twice, however Enbrel had to be administered every other day for the 28 day study period (as indicated for Enbrel use).
The extent of disease, as measured by deformation of foot joints (Arthritic Index (AI) score), of untreated animals and any improvements resulting from CEL-2000 and Enbrel treated animal were then compared. In another study, CEL-2000 was administered five times over a 70 day period and the animals were monitored for a total study period of 90 days. In each case, CEL-2000 treatment proved effective in blocking progression of disease (RA) with statistically significant reduction in AI score compared to controls.
The CEL-2000 treatment was deemed safe and well tolerated without any reported adverse effects related to treatment. The CEL-2000 treatment appeared to change the course of the immune response in the diseased (RA) animals, limiting the development of the destructive action of Th17 and tumor necrosis factor alpha (TNF-alpha). Analysis of serum levels of 21 cytokines/chemokines after 10 days of CEL-2000 treatment indicated reductions in the characteristic cytokine markers of rheumatoid arthritis, TNF-alpha and IL-17, as well as IL-6, and MCP-1. A number of cytokine changes were also seen with Enbrel treatment, but to a lesser degree than that seen with CEL-2000 treatment.
CEL-2000 may also provide a number of potential benefits over existing rheumatoid arthritis treatments, such as Enbrel. It is also potentially a more disease-type specific therapy, should be significantly less expensive to manufacture, and could also be useful for patients who are not able to take or who may be unresponsive to other existing anti-arthritis therapies.
The research featured the team of collaborators from different disciplines bringing to the project the expertise of several different animal models of arthritis (Washington Biotech), long time association with modern molecular therapies and evaluation for RA (Bolder Biopath), experience with other LEAPS immunogens, and experience and expertise studying cytokines and with mechanistic studies of the LEAPS technology (NEOUCOMP), and peptide technologies (21st Century Biochemicals) to complement the expertise of the CEL-SCI researchers.