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Orally administered L. lactis secreting an anti-TNF Nanobody demonstrate efficacy in chronic colitis

(2010) MUCOSAL IMMUNOLOGY. 3(1). p.49-56
Author
Organization
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal disorder. Systemic treatment of IBD patients with anti-tumor necrosis factor (TNF)-alpha antibodies has proven to be a highly promising approach, but several drawbacks remain, including side effects related to systemic administration and high cost of treatment. Lactococcus lactis was engineered to secrete monovalent and bivalent murine (m) TNF-neutralizing Nanobodies as therapeutic proteins. These therapeutic proteins are derived from fragments of heavy-chain camelid antibodies and are more stable than conventional antibodies. L. lactis-secreted anti-mTNF Nanobodies neutralized mTNF in vitro. Daily oral administration of Nanobody-secreting L. lactis resulted in local delivery of anti-mTNF Nanobodies at the colon and significantly reduced inflammation in mice with dextran sulfate sodium (DSS)-induced chronic colitis. In addition, this approach was also successful in improving established enterocolitis in interleukin 10 (IL10)(-/-) mice. Finally, L. lactis-secreted anti-mTNF Nanobodies did not interfere with systemic Salmonella infection in colitic IL10(-/-) mice. In conclusion, this report details a new therapeutic approach for treatment of chronic colitis, involving in situ secretion of anti-mTNF Nanobodies by orally administered L. lactis bacteria. Therapeutic application of these engineered bacteria could eventually lead to more effective and safer management of IBD in humans.
Keywords
ULCERATIVE-COLITIS, HUMAN-MONOCYTES, FACTOR-ALPHA, CROHNS-DISEASE, MODIFIED LACTOCOCCUS-LACTIS, CHIMERIC MONOCLONAL-ANTIBODY, INFLAMMATORY-BOWEL-DISEASE, TUMOR-NECROSIS-FACTOR, INTERLEUKIN-10, INFLIXIMAB

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Chicago
Vandenbroucke, Klaas, H de Haard, E Beirnaert, T Dreier, M Lauwereys, Lynn Huyck, Jacques Van Huysse, et al. 2010. “Orally Administered L. Lactis Secreting an anti-TNF Nanobody Demonstrate Efficacy in Chronic Colitis.” Mucosal Immunology 3 (1): 49–56.
APA
Vandenbroucke, Klaas, de Haard, H., Beirnaert, E., Dreier, T., Lauwereys, M., Huyck, L., Van Huysse, J., et al. (2010). Orally administered L. lactis secreting an anti-TNF Nanobody demonstrate efficacy in chronic colitis. MUCOSAL IMMUNOLOGY, 3(1), 49–56.
Vancouver
1.
Vandenbroucke K, de Haard H, Beirnaert E, Dreier T, Lauwereys M, Huyck L, et al. Orally administered L. lactis secreting an anti-TNF Nanobody demonstrate efficacy in chronic colitis. MUCOSAL IMMUNOLOGY. NEW YORK: NATURE PUBLISHING GROUP; 2010;3(1):49–56.
MLA
Vandenbroucke, Klaas et al. “Orally Administered L. Lactis Secreting an anti-TNF Nanobody Demonstrate Efficacy in Chronic Colitis.” MUCOSAL IMMUNOLOGY 3.1 (2010): 49–56. Print.
@article{818056,
  abstract     = {Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal disorder. Systemic treatment of IBD patients with anti-tumor necrosis factor (TNF)-alpha antibodies has proven to be a highly promising approach, but several drawbacks remain, including side effects related to systemic administration and high cost of treatment. Lactococcus lactis was engineered to secrete monovalent and bivalent murine (m) TNF-neutralizing Nanobodies as therapeutic proteins. These therapeutic proteins are derived from fragments of heavy-chain camelid antibodies and are more stable than conventional antibodies. L. lactis-secreted anti-mTNF Nanobodies neutralized mTNF in vitro. Daily oral administration of Nanobody-secreting L. lactis resulted in local delivery of anti-mTNF Nanobodies at the colon and significantly reduced inflammation in mice with dextran sulfate sodium (DSS)-induced chronic colitis. In addition, this approach was also successful in improving established enterocolitis in interleukin 10 (IL10)(-/-) mice. Finally, L. lactis-secreted anti-mTNF Nanobodies did not interfere with systemic Salmonella infection in colitic IL10(-/-) mice. In conclusion, this report details a new therapeutic approach for treatment of chronic colitis, involving in situ secretion of anti-mTNF Nanobodies by orally administered L. lactis bacteria. Therapeutic application of these engineered bacteria could eventually lead to more effective and safer management of IBD in humans.},
  author       = {Vandenbroucke, Klaas and de Haard, H and Beirnaert, E and Dreier, T and Lauwereys, M and Huyck, Lynn and Van Huysse, Jacques and Demetter, P and Steidler, L and Remaut, Erik and Cuvelier, Claude and Rottiers, Pieter},
  issn         = {1933-0219},
  journal      = {MUCOSAL IMMUNOLOGY},
  language     = {eng},
  number       = {1},
  pages        = {49--56},
  publisher    = {NATURE PUBLISHING GROUP},
  title        = {Orally administered L. lactis secreting an anti-TNF Nanobody demonstrate efficacy in chronic colitis},
  url          = {http://dx.doi.org/10.1038/mi.2009.116},
  volume       = {3},
  year         = {2010},
}

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