Autologous attenuated T-cell vaccine (Tovaxin) dose escalation in multiple sclerosis relapsing-remitting and secondary progressive patients nonresponsive to approved immunomodulatory therapies.
An open-label dose escalation study of T-cell vaccination in multiple sclerosis patients was conducted using attenuated myelin reactive T-cells (MRTC) selected with six myelin peptides, two each from MBP, PLP and MOG. The dose range of subcutaneous injections given at weeks 0, 4, 12 and 20 was 6-9E6, 30-45E6 and 60-90E6 irradiated MRTC. Assessments were over 52 weeks for MRTC levels, EDSS, MSIS-29, brain MRI and relapses. The 30-45E6 dose was the most effective with reductions in MRTC ranging from 92.4% at week 5 to 64.8% at week 52. The reduction in relapses compared to baseline for the M-ITT and evaluable per-protocol analyses were 63.5%, and 85.0% at week 52. The MRI lesions were stable while there was an improvement trend in the EDSS and MSIS-29 physical subscore following the second injection. Adverse events were mild to moderate in intensity with mild injection site reactions occurring with increasing dosage. The mid-dose was selected for further clinical development studies because of the rapid depletion of peripheral blood MRTC and a trend for improvements in clinical outcomes following immunization.
Loftus
B
B
Bellaire Neurology, Bellaire, TX 77401, USA.
Newsom
B
B
Montgomery
M
M
Von Gynz-Rekowski
K
K
Riser
M
M
Inman
S
S
Garces
P
P
Rill
D
D
Zhang
J
J
Williams
J C
JC
D000328:Adult; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007167:Immunotherapy / Q000592:standards; D055104:Infusions, Subcutaneous; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000503:physiopathology; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D014612:Vaccines; D014613:Vaccines, Attenuated / Q000627:therapeutic use*; D022223:Vaccines, Subunit / Q000009:adverse effects / Q000627:therapeutic use*
D007155:Immunologic Factors; D004676:Myelin Basic Protein; D014612:Vaccines; D014613:Vaccines, Attenuated; D022223:Vaccines, Subunit; C540587:tovaxin