This is a randomized, double blind phase II trial of a T cell vaccine in patients with secondary progressive multiple sclerosis (SP-MS). This study is based on encouraging data in 4 SP-MS patients with EDSS of 5.5-6.5 at time of entry. They received their own T cells cultured for 6-8 weeks in whole bovine myelin proteins followed by radiation prior to injection. Patients have been in the study up to 27 months. All will complete vaccination at 24 months. No adverse effects have been seen. T cell frequencies to bovine myelin used for vaccine production are undetectable (less than 1 per 106 cells) and responses to peptides of MBP, MOG and PLP are similar. Cytotoxicity to the Bovine myelin specific T cells can be demonstrated and marked reduction in IL-2 and IFN-gamma production can also be demonstrated. EDSS is stable with some improvement in 2 patients. Unblinded MRI s of the brain in 3 of 4 patients show no new gadilidium enhancing lesions, no increase in number or volume. One patient has at 6 months shown a single new lesion in the brain.
Specific aims of this study is (1) to determine if T cell vaccine stimulated and expanded by the broadest antigenic exposure (bovine myelin) will prevent MRI activity (2) to determine if elimination or inactivation of myelin specific T cells will correlate with clinical effects (EDSS and Quantitative Functional Composite (QFC)) and MRI analysis in the 24 months the vaccine is delivered and the 12 month follow-up. We also would like to determine if there is epitope spreading, as has been found when more specific vaccines (MBP-specific T cells or T cell receptor peptides) have been used. 2x40 patients will be studies for 36 months. This study, by design, will determine if MRI activity is decrease and correlates with trends toward clinical efficacy. Safety, and the importance of myelin specific T cell responses in SP-MS will also be determined.
| Lund, Brett T; Ashikian, Nazely; Ta, Huy Q et al. (2004) Increased CXCL8 (IL-8) expression in Multiple Sclerosis. J Neuroimmunol 155:161-71 |
