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Protein therapeutics, like vaccines, tend to induce immune responses if administered more than once. This immune response can interfere with the effect (or the effectiveness) of a therapeutic treatment. In clinical practice, physicians will change the type of drug that they administer or give immunosuppressive drugs along with the drug. In either case, the net effect is that the patient’s choices of therapy are restricted, or the drug stops working entirely, and, in some cases, the patients may develop severe side effects.

For most pharmaceutical companies, the effect of immunogenicity is to reduce market share, and for patients it may mean a relapse of their disease or a limit on the number of effective clinical treatments. In addition, protein therapeutics can be associated with severe types of immune response such as anemia, as was seen with a Centocor-produced erythropoietin marketed in Europe (Eprex). Eprex-associated immunogenicity resulted in the discontinuation of one formulation of the product.

While conducting its usual business of screening protein therapeutics for its clients, EpiVax discovered Tregitope, a peptide that has the potential to revolutionize protein therapeutics research and development efforts. This key compound induces tolerance to any protein with which it is co-administered. This is significant because it has the potential to reduce the number of catastrophic or even deadly effects of some medications used to treat chronic diseases and illnesses that affect hundreds of thousands of patients around the world. Tregitope is a peptides that triggers a natural “suppressive” immune response. This response is due to the fact that Tregitope is recognized by regulatory T cells. Also known as Tregs, these cells are the key controllers of inflammation and “effector” immune response.

Immune responses are also at the root of autoimmune disease. For example, in most patients with Type 1 Diabetes, immune responses to the body’s insulin protein diminishes insulin production, and thus blood sugar is not properly regulated. The insulin protein can be produced in the laboratory and administered as therapy, but this requires frequent injections for life.

Similarly, Graves’ disease (a thyroid condition), Multiple Sclerosis (MS) and even cardiovascular disease (associated with a higher risk of heart attacks) are associated with autoimmune response. Tregitope is being tested in animal models of these conditions and appears to have great promise.

One of the most exciting applications of Tregitope is in Transplantation. If Tregitope works as expected, it might be used to induce chimerism (a tolerant state) following the transplantation of a donor organ; patients who receive new livers, lungs, bone marrow or hearts would no longer have to be on immunosuppressive therapy. Collaborators Nader Najafian and Francesca D’Addio (Harvard Brigham and Women’s Hospital) won a prize for the presentation of their research on Tregitope in a murine model of transplantation at the 2009 meeting of the American Transplant Society.

The potential for Tregitope to modify the course of human disease has also been recognized by EpiVax’ scientific peers. Thus far, EpiVax has received funding of more than $1.5 million from such organizations as the National Institutes for Health (NIH) ($1M), Juvenile Diabetes Research Foundation (JDRF) ($400,000), and the Montel Williams Foundation ($35,000). All of these grants were awarded within the first year of the discovery of the Tregitope molecule, which in turn indicates a serious interest within the research and development community (i.e., through the use of both federal government and private foundation funds) to support further evaluation of the molecule.

In December 2009, Roche, a large global pharmaceutical company, established a strategic alliance with EpiVax which will result in further development of the Tregitope technology. Please stay tuned for more updates on this exciting discovery.