Original articleA Phase I Trial With Transgenic Bacteria Expressing Interleukin-10 in Crohn’s Disease
Section snippets
Patient Selection and Treatment Regime
Patients were screened for eligibility 1 week before enrollment, once informed consent had been obtained. Eligible patients had Crohn’s disease, confirmed by routine endoscopic and histologic examination, for at least 3 months’ duration and a score on the CDAI ranging from 220–450. The CDAI incorporates 8 variables related to the disease activity: the number of liquid or very soft stools, the severity of abdominal pain or cramping, general well-being, the presence of extraintestinal
Study Design
The Medical Ethical Commission of the Academic Medical Center and the Dutch Administration of Public Health, Environment and Nature approved a limited clinical trail with LL-Thy12 in patients under physical containment (http://www.cogem.net). This study aimed at evaluating clinical as well as environmental safety of LL-Thy12. In total, 10 patients with moderate to severe Crohn’s disease (see Supplemental Table 1 at www.cghjournal.org) were included in the study. All patients were admitted to an
Discussion
We conducted the first human trial with a genetically engineered, therapeutic bacterium, and the results obtained indicate that such a strategy can be both safe for the patient as well as biologically contained. Such therapy encompasses important advances compared with current systemic treatment.
The clinical parameters obtained, including the assessment of adverse events and scoring for disease activity, showed that the topical application of recombinant proteins by L lactis–mediated delivery
References (20)
- et al.
Advances in the treatment of Crohn’s disease
Gastroenterology
(2004) - et al.
Interleukin-10-deficient mice develop chronic enterocolitis
Cell
(1993) - et al.
Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn’s diseasethe Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group
Gastroenterology
(2000) - et al.
Endoscopy in inflammatory bowel diseases
Gastroenterology
(2004) - et al.
Development of an enteric-coated formulation containing freeze-dried, viable recombinant Lactococcus lactis for the ileal mucosal delivery of human interleukin-10
Eur J Pharm Biopharm
(2005) - et al.
Development of a Crohn’s disease activity indexNational Cooperative Crohn’s Disease Study
Gastroenterology
(1976) - et al.
Active delivery of trefoil factors by genetically modified Lactococcus lactis prevents and heals acute colitis in mice
Gastroenterology
(2004) Beyond pills and jabsresearchers develop new ways to get drugs to the right place at the right time
Lancet
(2003)- et al.
The immunological and genetic basis of inflammatory bowel disease
Nat Rev Immunol
(2003) - et al.
A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s diseaseCrohn’s Disease cA2 Study Group
N Engl J Med
(1997)
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H.B. was supported by the Broad Medical Research Program. D.W.H. is Clinical Fellow of The Netherlands Organization for Health Research and Development. The Science Foundation Ireland (SFI/01/F.1/B036) partly supported L.S. and S.N. M.P. is supported by the “Maag Lever Darm Stichting.” P.R is supported by the Flanders Interuniversity Institute for Biotechnology. E.R., N.H., and J.P.R. are supported by the Research Fund of Ghent University (GOA project no. 12050700).