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.
TRANSLATIONAL RESEARCHNew Therapies for MSDennis Bourdette, M.D. and Arthur A. Vandenbark, Ph.D.
TCR peptide therapy
Recombinant TCR ligand (RTL) therapy
Therapeutic Vaccination of MS Patient
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 StableWorse
P < 0.001
Strong Response:> 8 cells/million
Moderate Response: 2 - 8 cells/million
Conclusions: TCR Peptide Therapy
RTL (Recombinant TCR Ligand) Therapy for MS
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
Treatment of Relapsing EAE with RTLs
Conclusions: RTL Therapy