T-cell Vaccination
Patent number 6,303,314, issued on October 16, 2001, entitled "T cell receptor (TCR) VB DB JB Sequence and Methods for its Detection" describes an oligonucleotide sequence which codes for peptides expressed on T cells that are present in approximately 41% of patients with multiple sclerosis. This analysis was done specifically using complementarity- determining-region 3 (CDR3) sequence analysis. An office action is pending on a Continuation-In-Part (CIP) application.

Human Monoclonal Antibody
In Patent number 6,303,314, issued on October 16, 2001, entitled T cell receptor (TCR) VB-DB-JB Sequence and Methods for its Detection, we describe an oligonucleotide sequence which codes for peptides expressed on T cells. Although this patent covers a sequence that is expressed in approximately 41% of patients, Opexa has identified additional sequences that are expressed in up to 88% of MS patients. A patent application for these additional peptide sequences has been filed. Human monoclonal antibodies that are immunoreactive with these TCR peptide sequences can be produced. These monoclonal antibodies could be administered therapeutically to target and destroy autoreactive T cells in MS patients. A monoclonal antibody therapy is a well-accepted approach by both regulatory authorities and patients. From a practical standpoint, a monoclonal antibody therapeutic may be developed relatively quickly since the antigen target has been identified. Opexa is currently in collaborative discussions with companies that can produce human monoclonal antibodies.

Peptide-based Vaccine
The same common motif TCR peptide sequences used to develop the therapeutic monoclonal antibody may be developed for use as a peptide- based vaccine. With this product, the patient's immune system would be induced to produce an immune response that would specifically target autoreactive T cells expressing the common motif TCR peptide sequence on their surface. This vaccine is advantageous because it targets MS at the molecular level rather than the cellular level. Targeting at the molecular level avoids damage to uninvolved cells and reduces or eliminates side effects associated with many current MS treatments.

The National Institute of Health has shown interest in peptide-based vaccines and has awarded a $1 million grant to Dr. Zhang for continued research at the Baylor College of Medicine. In this project, Dr. Zhang is identifying the dominant idiotypic epitopes responsible for eliciting anti-idiotypic immune responses in T cell vaccination. The study is designed to evaluate whether TCR hyper-variable regions most frequently used among autoreactive T cells in MS patients contain dominant idiotypic epitopes for anti-idiotypic T and B cells and whether TCR peptides consisting of these identified dominant epitopes are effective in inhibiting autoreactive T cells by up-regulating anti-idiotypic immune responses. Zhang has thus far been successful in identifying 4 peptide epitopes, and, as mentioned above, at least one of these sequences is present on the T cells of up to 88% of MS patients examined.

The peptide-based vaccine is currently in the preclinical stage of development.