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T-cell vaccination (TCV) is a unique approach to induce immune regulation that may have importance in the treatment of autoimmune diseases, including multiple sclerosis (MS). TCV employs a classic vaccine strategy of injecting an attenuated form of the disease-causing agent--in this case, myelin-reactive T cells--that have been selected and expanded from each MS donor and then re-injected after irradiation to induce protective immunity. This anti-T-cell immunity consistently results in selective deletion or regulation of the targeted pathogenic T cells in vivo. Longitudinal studies have established that TCV is safe and often results in a reduced relapse rate and clinical stability or improvement, at least temporarily, in the majority of treated MS patients. These results lend direct support to the involvement of inflammatory myelin-reactive T cells in the MS disease process. However, these hopeful trends reported in a number of pilot trials await validation in larger proof-of-principle trials that are now in progress.

BackgroundT-cell vaccination (TCV) for multiple sclerosis (MS) refers to treatment with autologous anti-myelin T-cells, attenuated by irradiation. Previously published clinical trials have been all open-labeled.AimTo evaluate the safety and efficacy of TCV in progressive MS, in a double-blind, controlled clinical trial.MethodologyTwenty-six patients with relapsing-progressive MS were enrolled in the study (mean age: 39±9.8 years; mean EDSS: 4.4±1.7). T-cell lines reactive to 9 different peptides of the myelin antigens, MBP, MOG and PLP were raised from the patients' peripheral blood. The patients were randomized into two groups: 19 were treated with TCV (four subcutaneous injections of 10–30×106 T-cells, attenuated by irradiation, on days 1, 30, 90 and 180) and 7 patients were treated with sham injections. Twenty-four patients (17 in the TCV group and 7 in the placebo) were eligible for per-protocol analysis.ResultsAt one year following the inclusion, an increase in the EDSS (+0.50) and an increase in 10-meter walking time (+0.18 sec), were observed in the placebo group; in the TCV group there was a decrease in the EDSS (−0.44; p<0.01) and in the 10-meter walking time (0.84 sec; p<0.005). Sixteen of the 17 patients (94.1%) in the TCV group remained relapse-free during the year of the study, as compared to 42.9% in the placebo group (p = 0.01 and p = 0.03 with adjustment). The proportion of patients with any relapse during the year of the study in the TCV-group, was reduced by 89.6%., as compared to the placebo-treated group. MRI parameters did not change significantly.ConclusionsThis is the first controlled, double-blind trial with TCV in progressive MS. The results demonstrate the feasibility and safety of the procedure, and provide significant indications of clinical efficacy. Further studies with larger groups of subjects are warranted.Trial RegistrationClinicalTrials.gov NCT01448252