#MSBlog: A first for the T-cell vaccination lobby; a double-blind controlled trial! Time for a celebration?
BACKGROUND: T-cell vaccination (TCV) for MS refers to treatment with autologous anti-myelin T-cells, attenuated by irradiation. Previously published clinical trials have been all open-labeled.
AIM: To evaluate the safety and efficacy of TCV in progressive MS, in a double-blind, controlled clinical trial.
METHODOLOGY: 26 relapsing-progressive MSers 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 MSers' peripheral blood. The MSers were randomized into two groups: 19 were treated with TCV (four subcutaneous injections of 10-30×10(6) T-cells, attenuated by irradiation, on days 1, 30, 90 and 180) and 7 MSers were treated with sham injections. Twenty-four MSers (17 in the TCV group and 7 in the placebo) were eligible for per-protocol analysis.
RESULTS: At 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 MSers (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 MSers 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.
CONCLUSIONS: This 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 REGISTRATION: ClinicalTrials.gov NCT01448252.
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"The results of this study are a first, i.e. the first double-blind, controlled clinical trial of T cell vaccination in MS and they are positive. What is T-cell vaccination? The investigators' take T cells from the blood of MSers and then expand their numbers, i.e. grow them in the lab, by stimulating them with putative autoantigens. They then irradiate them to stop them dividing and then inject them back into the blood stream of the MSer. The idea is that the immune system sees these cells as foreign and mount an immune attack against them. By doing this the immune system then destroys other autoreactive cells. Is sounds simple, but the immune system usually bounces back with new T cells that have not been included in the vaccine pool."
"I don't want to spoil the party, but I doubt this approach will work. Firstly, it is based on the premise that MS is an autoimmune disease. I have argued before that I don't think MS is autoimmune. The target antigens are MBP, MOG and PLP; why these antigens? These antigens are immunogenic in animals and induce EAE, but the evidence that they play a role in MS is circumstantial. In fact the auto-antigen in MS remains undefined. Finally, this study is very small and underpowered. Therefore the the odds are the results are likely to be a false-positive. Let's hope I am wrong and that a larger follow-on study is done!"