Autologous attenuated T-cell vaccine (Tovaxin) dose escalation in multiple sclerosis relapsing-remitting and secondary progressive patients nonresponsive to approved immunomodulatory therapies

Clin Immunol. 2009 May;131(2):202-15. doi: 10.1016/j.clim.2009.01.005. Epub 2009 Feb 18.

Abstract

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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Dose-Response Relationship, Drug
  • Humans
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use*
  • Immunotherapy* / standards
  • Infusions, Subcutaneous
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / physiopathology
  • Myelin Basic Protein / genetics
  • Myelin Basic Protein / immunology
  • T-Lymphocytes / immunology*
  • Treatment Outcome
  • Vaccines
  • Vaccines, Attenuated / therapeutic use*
  • Vaccines, Subunit / adverse effects
  • Vaccines, Subunit / therapeutic use*

Substances

  • Immunologic Factors
  • Myelin Basic Protein
  • Vaccines
  • Vaccines, Attenuated
  • Vaccines, Subunit
  • tovaxin