Affiliation:
1. CNRS Enzyme and Cell Engineering Laboratory Université de Technologie de Compiègne Rue du Docteur Schweitzer, CS 60319 60203 Compiègne Cedex France
2. Global CMC Early Development Synthetics Platform Sanofi-Aventis Deutschland GmbH Industrial Park Hoechst, Building G849 65926 Frankfurt/Main Germany
3. Global CMC Early Development Synthetics Platform Sanofi Global R&D 350 Water Street Cambridge MA 02141 USA
Abstract
AbstractTumor Necrosis Factor‐α (TNF‐α) is a cytokine that is normally produced by immune cells when fighting an infection. But, when too much TNF‐α is produced as in autoimmune diseases, this leads to unwanted and persistent inflammation. Anti‐TNF‐α monoclonal antibodies have revolutionized the therapy of these disorders by blocking TNF‐α and preventing its binding to TNF‐α receptors, thus suppressing the inflammation. Herein, we propose an alternative in the form of molecularly imprinted polymer nanogels (MIP‐NGs). MIP‐NGs are synthetic antibodies obtained by nanomoulding the 3‐dimensional shape and chemical functionalities of a desired target in a synthetic polymer. Using an in‐house developed in silico rational approach, epitope peptides of TNF‐α were generated and ‘synthetic peptide antibodies’ were prepared. The resultant MIP‐NGs bind the template peptide and recombinant TNF‐α with high affinity and selectivity, and can block the binding of TNF‐α to its receptor. Consequently they were applied to neutralize pro‐inflammatory TNF‐α in the supernatant of human THP‐1 macrophages, leading to a downregulation of the secretion of pro‐inflammatory cytokines. Our results suggest that MIP‐NGs, which are thermally and biochemically more stable and easier to manufacture than antibodies, and cost‐effective, are very promising as next generation TNF‐α inhibitors for the treatment of inflammatory diseases.
Funder
Institut Universitaire de France
Sanofi-Aventis Deutschland
Cited by
1 articles.
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