title: T cell vaccination benefits relapsing progressive multiple sclerosis patients: a randomized, double-blind clinical trial.
abstract: BACKGROUND
  T-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.
  
  
  OBJECTIVE
  To evaluate the safety and efficacy of TCV in progressive MS, in a double-blind, controlled clinical trial.
  
  
  METHODS
  Twenty-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 10-30×10(6) 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.
  
  
  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 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.
  
  
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01448252.
authors.affiliation: Department of Neurology, MS Center and the Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Hospital, Jerusalem, Israel. karus@cc.huji.ac.il
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Karussis
authors.forename: Hagai
authors.initials: H
authors.lastname: Shor
authors.forename: Julia
authors.initials: J
authors.lastname: Yachnin
authors.forename: Naama
authors.initials: N
authors.lastname: Lanxner
authors.forename: Merav
authors.initials: M
authors.lastname: Amiel
authors.forename: Keren
authors.initials: K
authors.lastname: Baruch
authors.forename: Yael
authors.initials: Y
authors.lastname: Keren-Zur
authors.forename: Ofra
authors.initials: O
authors.lastname: Haviv
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
authors.forename: Panayiota
authors.initials: P
authors.lastname: Petrou
authors.forename: Shalom
authors.initials: S
authors.lastname: Hajag
authors.forename: Urania
authors.initials: U
authors.lastname: Vourka-Karussis
authors.forename: Adi
authors.initials: A
authors.lastname: Vaknin-Dembinsky
authors.forename: Salim
authors.initials: S
authors.lastname: Khoury
authors.forename: Oded
authors.initials: O
authors.lastname: Abramsky
authors.forename: Henri
authors.initials: H
authors.lastname: Atlan
authors.forename: Irun R
authors.initials: IR
authors.lastname: Cohen
authors.forename: Rivka
authors.initials: R
authors.lastname: Abulafia-Lapid
mesh_terms: D000328:Adult; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D020528:Multiple Sclerosis, Chronic Progressive / Q000628:therapy*; D009186:Myelin Sheath / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D010919:Placebos; D012008:Recurrence; D013601:T-Lymphocytes / Q000166:cytology*; D013997:Time Factors; D014611:Vaccination
chemical_list: D010455:Peptides; D010919:Placebos