Drs. Dépis, Kosco-Vilbois, and Dean are coinventors on a patent filed by NovImmune SA for combination therapies and methods using anti-CD3–modulating agents and anti-TNF antagonists (PCT/US2010/1035081).
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Experimental Arthritis
Long-term amelioration of established collagen-induced arthritis achieved with short-term therapy combining anti-CD3 and anti–tumor necrosis factor treatments
Article first published online: 27 SEP 2012
DOI: 10.1002/art.34497
Copyright © 2012 by the American College of Rheumatology
Additional Information
How to Cite
Dépis, F., Hatterer, E., Lamacchia, C., Waldburger, J.-M., Gabay, C., Reith, W., Kosco-Vilbois, M. and Dean, Y. (2012), Long-term amelioration of established collagen-induced arthritis achieved with short-term therapy combining anti-CD3 and anti–tumor necrosis factor treatments. Arthritis & Rheumatism, 64: 3189–3198. doi: 10.1002/art.34497
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Drs. Dépis, Kosco-Vilbois, and Dean are coinventors on a patent filed by NovImmune SA for combination therapies and methods using anti-CD3–modulating agents and anti-TNF antagonists (PCT/US2010/1035081).
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Drs. Hatterer, Reith, Kosco-Vilbois, and Dean own stock or stock options in NovImmune SA.
Publication History
- Issue published online: 27 SEP 2012
- Article first published online: 27 SEP 2012
- Accepted manuscript online: 16 APR 2012 09:30AM EST
- Manuscript Accepted: 3 APR 2012
- Manuscript Received: 25 OCT 2011
Funded by
- NovImmune SA
- Swiss National Science Foundation. Grant Numbers: 310030-135195, 310030-122477, 31003A-127255
- Albert Böni Foundation
- Carlos et Elise de Reuters Foundation
- Institute for Arthritis Research
- Abstract
- Article
- References
- Cited By
Abstract
Objective
The goal of rheumatoid arthritis (RA) treatment is to achieve clinical remission in order to limit structural damage and physical disability. To this end, recent emphasis has been placed on aggressive treatment early in the course of disease with drugs such as anti–tumor necrosis factor (anti-TNF) agents. As T cells are also thought to play an important role in the initiation of RA, we hypothesized that targeting both TNF and T cells would result in better outcomes. The aim of this study was to examine the efficacy of combined therapy with anti-CD3 and anti-TNF in experimental RA.
Methods
Two anti-mouse antibodies were developed as surrogate reagents for anti-TNF and anti-CD3 therapies. Collagen-induced arthritis (CIA) was induced in DBA/1 mice, and antibodies were injected intraperitoneally, either alone on in combination, at predetermined subtherapeutic doses. The frequency and number of pathogenic and regulatory CD4+ T cell subsets in the draining lymph nodes were determined in order to investigate the mechanisms of action.
Results
Strikingly, the combination of the two antibodies demonstrated a potent synergy in established CIA, with long-term inhibition of disease progression and protection from joint destruction. The results did not demonstrate any enhancement of CD25+FoxP3+ regulatory T cells, but a profound depletion of pathogenic T cells from the draining lymph nodes was associated with reduced numbers of T cells in the joints.
Conclusion
A short course of combination therapy with anti-CD3 and anti-TNF efficiently depletes pathogenic T cells from the draining lymph nodes, reducing the numbers of T cells in the joints and affording long-lasting inhibition of established CIA.