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

Mucosal Immunol. 2010 Jan;3(1):49-56. doi: 10.1038/mi.2009.116. Epub 2009 Sep 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antibodies, Bispecific / administration & dosage
  • Antibodies, Bispecific / genetics
  • Cell Line
  • Chronic Disease
  • Colitis / chemically induced
  • Colitis / drug therapy
  • Colitis / immunology*
  • Colitis / physiopathology
  • Dextran Sulfate / administration & dosage
  • Female
  • Genetic Engineering
  • Lactococcus lactis / genetics
  • Lactococcus lactis / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Nanoparticles / administration & dosage
  • Tumor Necrosis Factor-alpha / immunology*


  • Antibodies, Bispecific
  • Tumor Necrosis Factor-alpha
  • Dextran Sulfate