V-BETA-17 T-CELL RECEPTOR PEPTIDE VACCINATION IN RHEUMATOID-ARTHRITIS- RESULTS OF PHASE-I DOSE-ESCALATION STUDY

Objective. To determine whether modulation of activated T cells occurs in patients with rheumatoid arthritis (RA) after immunization with T cell receptor (TCR) V beta 17 peptides, a phase I trial was initiated to investigate the safety and feasibility of TCR peptide immunization as a therapeutic approach in RA.Methods. 15 patients with moderate to severe RA were given an intramuscular injection of one of 4 doses (10, 30, 100, and 300 mu g) of the V beta 17 peptide vaccination, followed by a booster injection of the same dose of vaccine 3 weeks later. Pat ients were followed for 48 weeks. Results. The product was well tolera ted and no serious adverse events attributable to the vaccine were obs erved. This was an uncontrolled phase I trial, however; decreases in p atient joint scores were observed at all followup visits starting at 4 weeks after primary immunization, Activated V beta 17 T cells (IL-2R) in peripheral blood were decreased (greater than or equal to 20%) in 3/5 patients in the 100 mu g group after initial measurement at Week 2 and 3/4 patients in the 300 mu g group 3 weeks after immunization. L ymphocyte proliferation in response to the V beta 17 peptide was detec ted at 6 weeks or later after primary inoculation in 6/15 patients (40 %) immunized. Conclusion. Further controlled studies are required to a ssess the biologic and clinical efficacy of this treatment approach.