Autologous antigen-specific regulatory T cells (TREG) are a well-tolerated potential therapy for refractory IBD, according to researchers from France.
Jean-Frédéric Colombel and colleagues carried out a 12-week, open-label, multicentre, single injection, escalating dose phase I and IIa clinical trial to investigate the safety and efficacy of ovalbumin-specific TREG (ova-TREG) cells as a treatment for IBD. The researchers recruited 20 patients with refractory Crohn's disease, and isolated TREG cells from their peripheral blood for in vitro culture with ovalbumin. The ova-TREG cells were then injected back into the patients.
The principle underlying this treatment approach is that the ova-TREG cells—which have been primed in vitro to respond to ovalbumin—will encounter and respond to this common food antigen in the gut. “The cells then deliver a local immunomodulatory stimulus with the potential to control inflammation,” explains Colombel.
Although all patients experienced adverse events, they were only thought to be treatment-related in 11 patients and all were, ultimately, resolved. Serious adverse events were experienced by seven patients and all except one, who died of treatment-unrelated causes, recovered. The safety profile of this treatment is in line with other first-in-man studies of acute refractory Crohn's disease therapies.
Reduction of Crohn's disease activity occurred in 40% of all patients at 5 weeks and 8 weeks after injection. In the group receiving the lowest dose of cells, 75% had responses and marked reduction of Crohn's disease activity during the study period; 38% were in remission at 5 weeks and 25% were still in remission at 8 weeks.
The researchers are planning a placebo-controlled trial. “The new study is to show proof of efficacy and define the optimum therapeutic dose,” notes Colombel.
ORIGINAL RESEARCH PAPER
Desreumaux, P. et al. Safety and efficacy of antigen-specific regulatory T-cell therapy for patients with refractory Crohn's disease. Gastroenterology doi:10.1053/j.gastro.2012.07.116
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McLarnon, A. Regulatory T-cell therapy is a safe and well-tolerated potential approach for treating refractory Crohn's disease. Nat Rev Gastroenterol Hepatol 9, 559 (2012). https://doi.org/10.1038/nrgastro.2012.167
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DOI: https://doi.org/10.1038/nrgastro.2012.167