Mucosal delivery of Lactococcus lactis carrying an anti-TNF scFv expression vector ameliorates experimental colitis in mice

Chiabai, Maria José; Almeida, Juliana Franco; Azevedo, Mariana Gabriela Dantas de; Fernandes, Suelen Soares; Pereira, Vanessa Bastos; Castro, Raffael Júnio Araújo de; Jerônimo, Márcio Sousa; Sousa, Isabel Garcia; Vianna, Leonora Maciel de Souza; Miyoshi, Anderson; Bocca, Anamélia Lorenzetti; Maranhão, Andréa Queiroz; Brigido, Marcelo M.

doi:10.1186/s12896-019-0518-6

Cited by 26 publications

(13 citation statements)

References 63 publications

(69 reference statements)

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“…Lacto-scFv is the prokaryote Lactococcus lactis , subspecies cremoris MG1363, carrying an eukaryotic expression plasmid coding for a single-chain fragment variable (scFv) antibody against TNF-α in view of transforming the epithelial cells of the host [ 146 ]. This prokaryote is extensively studied, apathogenic and non-invasive [ 166 ].…”

Section: Preclinical Studies On Local Tnf-α Inhibitionmentioning

confidence: 99%

Review: Local Tumor Necrosis Factor-α Inhibition in Inflammatory Bowel Disease

et al. 2020

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Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by intestinal inflammation. Increased intestinal levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) are associated with disease activity and severity. Anti-TNF-α therapy is administered systemically and efficacious in the treatment of IBD. However, systemic exposure is associated with adverse events that may impede therapeutic treatment. Clinical studies show that the efficacy correlates with immunological effects localized in the gastrointestinal tract (GIT) as opposed to systemic effects. These data suggest that site-specific TNF-α inhibition in IBD may be efficacious with fewer expected side effects related to systemic exposure. We therefore reviewed the available literature that investigated the efficacy or feasibility of local TNF-α inhibition in IBD. A literature search was performed on PubMed with given search terms and strategy. Of 8739 hits, 48 citations were included in this review. These studies ranged from animal studies to randomized placebo-controlled clinical trials. In these studies, local anti-TNF-α therapy was achieved with antibodies, antisense oligonucleotides (ASO), small interfering RNA (siRNA), microRNA (miRNA) and genetically modified organisms. This narrative review summarizes and discusses these approaches in view of the clinical relevance of local TNF-α inhibition in IBD.

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Section: Preclinical Studies On Local Tnf-α Inhibitionmentioning

confidence: 99%

Review: Local Tumor Necrosis Factor-α Inhibition in Inflammatory Bowel Disease

et al. 2020

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“…In another study, L. lactis carrying the scFv expression vector was administered by gavage to mice with DSS-induced colitis. After 4 days of treatment, animals showed a significant improvement in histological score and disease activity index compared with those of untreated animals ( Chiabai et al, 2019 ). Namai et al (2020) showed L. lactis was able to deliver IL-1 antagonists.…”

Section: Oral Delivery Of Biologics In Ibd Treatmentmentioning

confidence: 99%

Oral Delivery of Biologics in Inflammatory Bowel Disease Treatment

Zhang

Michalowski

Beloqui

2021

Front. Bioeng. Biotechnol.

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Inflammatory bowel disease (IBD) has been posed as a great worldwide health threat. Having an onset during early adulthood, IBD is a chronic inflammatory disease characterized by remission and relapse. Due to its enigmatic etiology, no cure has been developed at the moment. Conventionally, steroids, 5-aminosalicylic acid, and immunosuppressants have been applied clinically to relieve patients’ syndrome which, unfavorably, causes severe adverse drug reactions including diarrhea, anemia, and glaucoma. Insufficient therapeutic effects also loom, and surgical resection is mandatory in half of the patients within 10 years after diagnosis. Biologics demonstrated unique and differentiative therapeutic mechanism which can alleviate the inflammation more effectively. However, their application in IBD has been hindered considering their stability and toxicity. Scientists have brought up with the concept of nanomedicine to achieve the targeted drug delivery of biologics for IBD. Here, we provide an overview of biologics for IBD treatment and we review existing formulation strategies for different biological categories including antibodies, gene therapy, and peptides. This review highlights the current trends in oral delivery of biologics with an emphasis on the important role of nanomedicine in the development of reliable methods for biologic delivery in IBD treatment.

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“…It was able to reduce the levels of pro-inflammatory cytokines (IL-12, IL-6) and increase the levels of IL-10 and IL-4 secreting regulatory cells ( Souza et al, 2016 ). Similarly, mucosal delivery of L. lactis carrying a pValac anti-TNFα scFv expression plasmid in a DSS-induced colitis mouse model significantly improved histological scores and the disease activity index compared to untreated animals ( Chiabai et al, 2019 ).…”

Section: Live Bacteria As Mucosal Dna Vaccine Delivery Systems: mentioning

confidence: 99%

Novel Strategies for Efficient Production and Delivery of Live Biotherapeutics and Biotechnological Uses of Lactococcus lactis: The Lactic Acid Bacterium Model

Tavares¹,

Jesus²,

Silva³

et al. 2020

Front. Bioeng. Biotechnol.

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Lactic acid bacteria (LAB) are traditionally used in fermentation and food preservation processes and are recognized as safe for consumption. Recently, they have attracted attention due to their health-promoting properties; many species are already widely used as probiotics for treatment or prevention of various medical conditions, including inflammatory bowel diseases, infections, and autoimmune disorders. Some LAB, especially Lactococcus lactis , have been engineered as live vehicles for delivery of DNA vaccines and for production of therapeutic biomolecules. Here, we summarize work on engineering of LAB, with emphasis on the model LAB, L. lactis . We review the various expression systems for the production of heterologous proteins in Lactococcus spp. and its use as a live delivery system of DNA vaccines and for expression of biotherapeutics using the eukaryotic cell machinery. We have included examples of molecules produced by these expression platforms and their application in clinical disorders. We also present the CRISPR-Cas approach as a novel methodology for the development and optimization of food-grade expression of useful substances, and detail methods to improve DNA delivery by LAB to the gastrointestinal tract. Finally, we discuss perspectives for the development of medical applications of recombinant LABs involving animal model studies and human clinical trials, and we touch on the main safety issues that need to be taken into account so that bioengineered versions of these generally recognized as safe organisms will be considered acceptable for medical use.

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Mucosal delivery of Lactococcus lactis carrying an anti-TNF scFv expression vector ameliorates experimental colitis in mice

Cited by 26 publications

References 63 publications

Review: Local Tumor Necrosis Factor-α Inhibition in Inflammatory Bowel Disease

Review: Local Tumor Necrosis Factor-α Inhibition in Inflammatory Bowel Disease

Oral Delivery of Biologics in Inflammatory Bowel Disease Treatment

Novel Strategies for Efficient Production and Delivery of Live Biotherapeutics and Biotechnological Uses of Lactococcus lactis: The Lactic Acid Bacterium Model

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