AG013, a mouth rinse formulation of Lactococcus lactis secreting human Trefoil Factor 1, provides a safe and efficacious therapeutic tool for treating oral mucositis

Caluwaerts, Silvia; Vandenbroucke, Klaas; Steidler, Lothar; Neirynck, Sabine; Vanhoenacker, Peter; Corveleyn, Sam; Watkins, Brynmor A.; Sonis, Stephen T.; Coulie, Bernard; Rottiers, Pieter

doi:10.1016/j.oraloncology.2010.04.008

Cited by 118 publications

(75 citation statements)

References 20 publications

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“…Intragastric administration of TFF-secreting L. lactis to mice has also been proven to be effective in the prevention and healing of acute DSS-induced colitis and chronic colitis in IL-10-deficient mice (Vandenbroucke et al 2004). Because TFF-1 and -3 are also secreted by human salivary glands and thus present in saliva, an L. lactis strain secreting TFF-1 was recently formulated into a mouthwash for treatment of oral mucositis, a very common and painful complication of radio-or chemotherapy in cancer patients (Caluwaerts et al 2010). Cytotoxic anticancer drugs that affect fast-growing cancer cells also affect mucosal cells with their rapid mitotic rate, leading to atrophy, swelling, erythema, and ulceration (Raber-Durlacher et al 2010).…”

Section: Lab and Their Role In Delivering Cytokines And Other Moleculmentioning

confidence: 99%

“…Cytotoxic anticancer drugs that affect fast-growing cancer cells also affect mucosal cells with their rapid mitotic rate, leading to atrophy, swelling, erythema, and ulceration (Raber-Durlacher et al 2010). The TFF-1-secreting L. lactis strain was highly efficacious in alleviating oral mucositis in a hamster model (Caluwaerts et al 2010) and in patients in a phase 1b clinical trial, leading to a clinical phase 2/3 trial to begin in 2013 (http://www.actogenix.com).…”

Section: Lab and Their Role In Delivering Cytokines And Other Moleculmentioning

confidence: 99%

See 1 more Smart Citation

Probiotics: Properties, Examples, and Specific Applications

Behnsen

Deriu

Sassone‐Corsi

et al. 2013

Cold Spring Harbor Perspectives in Medicine

229

147

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Section: Lab and Their Role In Delivering Cytokines And Other Moleculmentioning

confidence: 99%

Section: Lab and Their Role In Delivering Cytokines And Other Moleculmentioning

confidence: 99%

Probiotics: Properties, Examples, and Specific Applications

Behnsen

Deriu

Sassone‐Corsi

et al. 2013

Cold Spring Harbor Perspectives in Medicine

229

147

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“…A preclinical study suggested that a mouth rinse with genetically modified bacteria engineered to secrete human TFF-1 may provide future management tools [94].…”

Section: Recommendations For Future Researchmentioning

confidence: 99%

Systematic review of cytokines and growth factors for the management of oral mucositis in cancer patients

Raber-Durlacher

Bültzingslöwen²,

Logan

et al. 2012

Support Care Cancer

113

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Purpose The aim of this project was to review the literature and define clinical practice guidelines for the use of cytokines and growth factor agents for the prevention or treatment of oral mucositis induced by cancer chemotherapy or radiotherapy. Care Cancer (2013) 21:343-355 DOI 10.1007/s00520-012-1594 following three guideline determinations was possible: Recommendation, Suggestion, No guideline possible. Results Sixty-four clinical studies across 11 interventions were evaluated. A recommendation was made for the use of recombinant human KGF-1 (palifermin) at a dose of 60 μg/kg per day for 3 days prior to conditioning treatment and for 3 days post-transplant for prevention of oral mucositis in patients receiving high-dose chemotherapy and total body irradiation followed by autologous stem cell transplantation for hematological malignancies. A suggestion was made against using granulocyte macrophage colony-stimulating factor mouthwash for the prevention of oral mucositis in the setting of high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation. No guideline was possible for any other cytokine or growth factor agents due to inconclusive evidence. Conclusions Of the cytokine and growth factor agents studied for oral mucositis, the evidence only supports use of palifermin in the specific population listed above. Additional welldesigned research is needed on other cytokine and growth factor interventions and in other cancer treatment settings. Methods

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“…This study showed promising results in murine models of IBD [11] and the bacterial strain has been tested in a phase 1 clinical trial by Actogenix (http://www.actogenix.com/). Lastly, L. lactis expressing human Trefoil Factor 1 (hTFF1) -a cytopeptide involved in epithelial wound healing -has been formulated as a mouthwash for the treatment of oral mucositis [12], which is a common complication found in patients that are subjected to chemo-and radiotherapies. This therapy has already passed through a phase 1 pharmacokinetic study and a phase 1b clinical trial involving cancer patients receiving chemotherapy, which showed alleviation of ulcerative oral mucositis symptoms in 30% of cases [13 ].…”

Section: Engineered Bacteria Against Inflammatory and Autoimmune Disomentioning

confidence: 99%

Engineered bacteria as therapeutic agents

Piñero-Lambea

Ruano-Gallego

Fernández

2015

Current Opinion in Biotechnology

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Although bacteria are generally regarded as the causative agents of infectious diseases, most bacteria inhabiting the human body are non-pathogenic and some of them can be turned, after proper engineering, into 'smart' living therapeutics of defined properties for the treatment of different illnesses. This review focuses on recent developments to engineer bacteria for the treatment of diverse human pathologies, including inflammatory bowel diseases, autoimmune disorders, cancer, metabolic diseases and obesity, as well as to combat bacterial and viral infections. We discuss significant advances provided by synthetic biology to fully reprogram bacteria as human therapeutics, including novel measures for strict biocontainment.

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AG013, a mouth rinse formulation of Lactococcus lactis secreting human Trefoil Factor 1, provides a safe and efficacious therapeutic tool for treating oral mucositis

Cited by 118 publications

References 20 publications

Probiotics: Properties, Examples, and Specific Applications

Probiotics: Properties, Examples, and Specific Applications

Systematic review of cytokines and growth factors for the management of oral mucositis in cancer patients

Engineered bacteria as therapeutic agents

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