کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3285363 | 1209227 | 2006 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A Phase I Trial With Transgenic Bacteria Expressing Interleukin-10 in Crohn's Disease
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Background & Aims: The use of living, genetically modified bacteria is an effective approach for topical delivery of immunomodulatory proteins. This strategy circumvents systemic side effects and allows long-term treatment of chronic diseases. However, treatment of patients with a living, genetically modified bacterium raises questions about the safety for human subjects per se and the biologic containment of the transgene. Methods: We treated Crohn's disease patients with genetically modified Lactococcus lactis (LL-Thy12) in which the thymidylate synthase gene was replaced with a synthetic sequence encoding mature human interleukin-10. Ten patients were included in a placebo-uncontrolled trial. Patients were assessed daily for the presence of potential adverse effects by direct questioning and assessment of disease activity. We evaluated the presence and kinetics of LL-Thy12 release in the stool of patients by conventional culturing and quantitative polymerase chain reaction of LL-Thy12 gene sequences. Results: Treatment with LL-Thy12 was safe because only minor adverse events were present, and a decrease in disease activity was observed. Moreover, fecally recovered LL-Thy12 bacteria were dependent on thymidine for growth and interleukin-10 production, indicating that the containment strategy was effective. Conclusions: Here we show that the use of genetically modified bacteria for mucosal delivery of proteins is a feasible strategy in human beings. This novel strategy avoids systemic side effects and is biologically contained; therefore it is suitable as maintenance treatment for chronic intestinal disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Clinical Gastroenterology and Hepatology - Volume 4, Issue 6, June 2006, Pages 754-759
Journal: Clinical Gastroenterology and Hepatology - Volume 4, Issue 6, June 2006, Pages 754-759
نویسندگان
Henri Braat, Pieter Rottiers, Daniel W. Hommes, Nathalie Huyghebaert, Erik Remaut, Jean-Paul Remon, Sander J.H. van Deventer, Sabine Neirynck, Maikel P. Peppelenbosch, Lothar Steidler,