好色先生

好色先生

Explore the latest content from across our publications

Log In

Forgot Password?
Create New Account

Loading... please wait

Abstract Details

Immune tolerance in patients with Multiple Sclerosis and Neuromyelitis Optica by peptide-loaded tolerogenic dendritic cells: final results of the phase 1b clinical trial and extension
Multiple Sclerosis
S56 - MS Trials and Treatment (1:11 PM-1:22 PM)
002
Multiple sclerosis (MS) and Neuromyelitis Optica Spectrum Disorders (NMOSD) are autoimmune diseases of the central nervous system leading to significant disability. The presence of autoimmune responses to myelin-derived peptides in MS and aquaporin-4 (AQP4) in NMOSD in humans support the development of antigen-specific tolerance induction therapies such as tolDCs. 

To verify the safety and signs of efficacy of the administration of tolerogenic dendritic cells (tolDCs) in patients with Multiple Sclerosis and Neuromyelitis optica spectrum disorder.

We conducted a first in human Phase Ib clinical trial testing increasing concentrations of autologous tolDCs (50 to 300 106 cells i.v. divided into 3 doses administered every 2 weeks) loaded with 7 myelin and one aquaporin-4 peptides in 12 patients, 8 with MS and 4 with NMOSD. The primary end-point was the safety and tolerability of the intervention and secondary end-points were clinical outcomes (relapses and disability), imaging (MRI and OCT) and immunological markers (cell subsets, cell proliferation and cytokine secretion for specific peptides). 

Therapy with tolDCs was well tolerated, without serious adverse events and with no therapy-related reactions. Patients remained stable at the clinical level in terms of relapses and disability scales, as well as at the imaging level. We observed a significant increase in the production of IL-10 levels in PBMCs stimulated with the peptides as well as an increase in the frequency of Tr1 cells by week 12 of follow-up. No significant differences were observed in terms of cell proliferation. These results were validated in 8 additional cases (5 MS and 3 NMO) treated with the higher dose, confirming the good tolerability of the therapy and the induction of immune tolerance by the treatment.

The intravenous administration of peptide-loaded DCs vaccination is safe, feasible and effective in eliciting antigen specific IL-10 production by T regulatory cells in MS and NMOSD patients.

Authors/Disclosures
Irati Zubizarreta
PRESENTER
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Albert Saiz (Hospital Clinico De Barcelona) Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janseen. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for novartis. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen.
Sara Llufriu Sara Llufriu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Sara Llufriu has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Sara Llufriu has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merci. Sara Llufriu has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbot. Sara Llufriu has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi.
No disclosure on file
No disclosure on file
No disclosure on file
Irene Pulido Valdeolivas No disclosure on file
No disclosure on file
No disclosure on file
Nieves Tellez Nieves Tellez has nothing to disclose.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Yolanda Blanco Morgado, MD Dr. Blanco Morgado has nothing to disclose.
Lawrence Steinman, MD, FAAN (Stanford Medicine) Dr. Steinman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TG Therapeutics. Dr. Steinman has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for 180 Life Sciences. Dr. Steinman has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for BioAtla. Dr. Steinman has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Pasithea. Dr. Steinman has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Atreca. Dr. Steinman has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Wilmer Hale Cutler Pickering. Dr. Steinman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Meyers Squibb. Dr. Steinman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Steinman has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for National Academy of Sciences. Dr. Steinman has received personal compensation in the range of $100,000-$499,999 for serving as an Expert Witness for Gibson Dunn. The institution of Dr. Steinman has received research support from Roche. The institution of Dr. Steinman has received research support from Novartis. Dr. Steinman has received intellectual property interests from a discovery or technology relating to health care.
No disclosure on file
Pablo Villoslada, MD, PhD, FAAN (Hospital del Mar Research Institute) Dr. Villoslada has received personal compensation for serving as an employee of Attune Neuroscience. Dr. Villoslada has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Accure Therapeutics. Dr. Villoslada has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Oculis. Dr. Villoslada has stock in Attune Neurosciences. Dr. Villoslada has stock in Bionure Investments. Dr. Villoslada has stock in Spiral Therapeutics. Dr. Villoslada has stock in Adhera Health. The institution of Dr. Villoslada has received research support from Start2Cure Foundation. The institution of Dr. Villoslada has received research support from NIH. The institution of Dr. Villoslada has received research support from Department of Defense. Dr. Villoslada has received intellectual property interests from a discovery or technology relating to health care.