The Multiple Sclerosis Center of Oregon
Where healing, teaching and discovery come together

Peptide Research

Our TCR peptide vaccination research program is attempting to develop a novel treatment for MS that seeks to stimulate the body's own natural mechanisms of controlling MS. Animal studies on TCR peptide vaccination started in 1988, and the Center's initial tests began in February 1992.

How does TCR peptide therapy work?

Our theory is that TCR peptides can act as a vaccine that teaches the patient's own immune system to control the disease-causing cells.  

The human body produces white blood cells, called T cells, that normally defend against infection. We believe a sub-population of T cells causes MS by attacking the brain's insulating material, or myelin.

We vaccinate patients against these attacking T cells, using a synthesized T cell component called a TCR peptide. When injected into a patient, the TCR peptide stimulates protective T cells and antibodies. In turn, these protective T cells and antibodies react against the attack T cells and inhibit them from causing disease.

What have we learned?

Several studies have shown positive results. We first studied TCR peptide vaccination in eleven patients with progressive MS in 1992. The results were published in the Journal of Immunology 1994, 152:2510-2519. We then performed a 23-patient placebo-controlled trial, which was published in Nature Medicine 1996, 2:1109-1115. These two studies indicated that we could stimulate protective T cells in about 50% of MS patients when we used a TCR peptide called substituted Vbeta5.2.

When patients were successfully vaccinated, the number of anti-myelin T cells in their blood decreased. The treatment appeared to be safe and well tolerated. Importantly, in the placebo-controlled trial, none of the patients who were successfully vaccinated with the substituted Vbeta5.2 TCR peptide were clinically worse after one year, while more than 50 percent of patients who received a placebo or who were not successfully vaccinated with peptide had clinically worsened.

Based on our initial results, a biotechnology company conducted a similar trial of TCR peptide vaccination in 106 MS patients at ten different MS clinics. This larger trial again suggested that the substituted Vbeta5.2 peptide could successfully stimulate protective T cells in close to half of patients and that it was safe.

What's next?

To prove the TCR peptide vaccination stops MS from progressing will require a very large and expensive research study. We believe there are several important questions to be answered before such a study can be done. We can only successfully vaccinate about 50 percent of MS patients using the substituted Vbeta5.2 peptide, and our goal is to be able to vaccinate 100 percent of patients.

We are looking at ways to improve our success rate. For example, we could use a substance that stimulates the immune system, or adjuvant, along with the TCR peptide. This might strengthen the response by the protective T cells and give us better results. Or we may need to use more than one TCR peptide, a TCR peptide "cocktail," to achieve better responses.

Finally, we would like to see whether successfully vaccinating patients with TCR peptides decreases MS disease activity on MRI. We need to study the effects of TCR peptide vaccination on MRI as part of our assessment.

Over the next few years our research team at the MS Center of Oregon will study the use of adjuvant and other TCR peptides that might be part of a "TCR peptide cocktail" and begin assessing the MRI effects of TCR peptide vaccination.

How is TCR peptide research funded?

Grants from the National Institutes of Health, the Department of Veterans Affairs and biotechnology companies have funded various aspects of our TCR peptide research program . Donations from private individuals also support the program. If you are interested in making a donation to support this or other research activities at the MS Center of Oregon, click here.