TRANSLATIONAL RESEARCH New Therapies for MS Dennis Bourdette, M.D. and Arthur A. Vandenbark, Ph.D. TCR peptide therapy Recombinant TCR ligand (RTL) therapy. Therapeutic Vaccination of MS Patient. Stimulus:. 100. TCR BV5S2 Peptide. Myelin Basic Protein. EDSS. 7. 6. 10. 5. 4.
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TCR peptide therapy
Recombinant TCR ligand (RTL) therapy
TCR BV5S2 Peptide
Myelin Basic Protein
LDA Frequency x 10-6
Weeks on Therapy
TCR Peptide VaccinationPilot Trials: Composite Phase I and II Studies
Responders Improved Stable Worse
Strong 3 1 0
Moderate 0 6 2
Non-Responders 1 6 13
P < 0.001
Strong Response: > 8 cells/million
Moderate Response: 2 - 8 cells/million
Arthur A. Vandenbark, Ph.D., Gregory G. Burrows, Ph.D., Halina Offner, Dr. Med., Dennis Bourdette, M.D.
Funded by NIH, NMSS, VA, Virogenomics
Responsive T Cell
β2 domain of MHC II contains key binding site for CD4 protein
1. Safe and effective in animal models of MS.
2. Specific target = fewer side effects
3. Platform to treat other inflammatory diseases (e.g. arthritis)
4. Attractive manufacturing and commercial properties
PRO-inflammatory cytokines are NOT released, causing a local reduction of T cell response in inflamed area
ANTI-Inflammatory cytokines (IL-10) released:
Portion of MHC II molecule; without lower a2 and b2chains
CD4 no longer binds, since it lacks the b2 domain of the MHC II. Thus, activation is altered
a2Effect of RTL on T Cell activation
Conclusions: RTL Therapy reduction of T cell response in inflamed area