title: Safety and efficacy of antigen-specific regulatory T-cell therapy for patients with refractory Crohn's disease.
abstract: OBJECTIVE
  New therapeutic strategies are needed for patients with refractory Crohn's disease (CD). We evaluated data from the Crohn's And Treg Cells Study (CATS1) to determine the safety and efficacy of antigen-specific T-regulatory (Treg) cells for treatment of patients with refractory CD.
  
  
  METHODS
  We performed a 12-week, open-label, multicenter, single-injection, escalating-dose, phase 1/2a clinical study in 20 patients with refractory CD. Ovalbumin-specific Treg cells (ova-Tregs) were isolated from patients' peripheral blood mononuclear cells (PBMCs), exposed to ovalbumin, and administrated intravenously. Safety and efficacy were assessed using clinical and laboratory parameters. We evaluated proliferation of PBMCs in response to ovalbumin.
  
  
  RESULTS
  Injections of ova-Tregs were well tolerated, with 54 adverse events (2 related to the test reagent) and 11 serious adverse events (3 related to the test reagent, all recovered). Overall, a response, based on a reduction in Crohn's Disease Activity Index (CDAI) of 100 points, was observed in 40% of patients at weeks 5 and 8. Six of the 8 patients (75%) who received doses of 10(6) cells had a response at weeks 5 and 8, with a statistically significant reduction in CDAI. In this group, remission (based on CDAI ≤150) was observed in 3 of 8 patients (38%) at week 5 and 2 of 8 patients (25%) at week 8.
  
  
  CONCLUSIONS
  Administration of antigen-specific Tregs to patients with refractory CD (CATS1) was well tolerated and had dose-related efficacy. The ovalbumin-specific immune response correlated with clinical response, supporting immune-suppressive mechanisms of ova-Tregs. The consistency of results among different assessment methods supports the efficacy of ova-Tregs; this immune therapy approach warrants further clinical and mechanistic studies in refractory CD. Eudract, Number: 2006-004712-44.
authors.affiliation: Department of Hepatogastroenterology and Centre d'Investigation Clinique, Huriez Hospital, Lille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Desreumaux
authors.affiliation: R&D, TxCell, Valbonne, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Foussat
authors.affiliation: Gastroenterology and Centre d'Investigation Clinique, Saint-Louis Hospital, Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Allez
authors.affiliation: Gastroenterology and Centre d'Investigation Clinique, St Antoine Hospital, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Beaugerie
authors.affiliation: Gastroenterology and Unité de Recherche Clinique, L'Archet 2 Hospital, Nice, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Hébuterne
authors.affiliation: Gastroenterology, Beaujon, Clichy, France.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Bouhnik
authors.affiliation: Gastroenterology and Centre d'Investigation Clinique, Jean Minjoz Hospital, Besançon, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Nachury
authors.affiliation: Clinical, TxCell, Valbonne, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Brun
authors.affiliation: R&D, TxCell, Valbonne, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Bastian
authors.affiliation: R&D, TxCell, Valbonne, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Belmonte
authors.affiliation: Immunology, L'Archet 1 Hospital, Nice, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Ticchioni
authors.affiliation: Manufacturing, TxCell, Valbonne, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Duchange
authors.affiliation: Centre Régina, Nice, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Morel-Mandrino
authors.affiliation: Effi-Stat, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Neveu
authors.affiliation: Clinical, TxCell, Valbonne, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Clerget-Chossat
authors.affiliation: Clinical, TxCell, Valbonne, France.
authors.forename: Miguel
authors.initials: M
authors.lastname: Forte
authors.affiliation: Department of Hepatogastroenterology and Centre d'Investigation Clinique, Huriez Hospital, Lille, France. Electronic address: jean-frederic.colombel@chru-lille.fr.
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Colombel
mesh_terms: D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D003424:Crohn Disease / Q000097:blood / Q000628:therapy*; D005243:Feces; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010047:Ovalbumin / Q000276:immunology; D011788:Quality of Life; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000637:transplantation*; D055815:Young Adult
chemical_list: D039841:Leukocyte L1 Antigen Complex; D010047:Ovalbumin; D002097:C-Reactive Protein