AI Article Synopsis

  • - Tumour necrosis factor (TNF) is a key pro-inflammatory cytokine linked to various inflammatory diseases, and its harmful effects can be countered using specific antagonists already approved for conditions like rheumatoid arthritis and psoriasis.
  • - A novel anti-TNF therapy has been developed using a single-domain monoclonal antibody (TNF-V(H) H) combined with an elastin-like polypeptide (ELP), which boosts production in transgenic tobacco plants.
  • - This plant-derived antibody demonstrated biological activity in vivo, successfully preventing death in humanized TNF mice due to septic shock, and had a significantly longer persistence compared to its non-ELPylated counterpart.

Article Abstract

Tumour necrosis factor (TNF) is a major pro-inflammatory cytokine involved in multiple inflammatory diseases. The detrimental activity of TNF can be blocked by various antagonists, and commercial therapeutics based upon this principle have been approved for treatment of diseases including rheumatoid arthritis, Crohn's disease and psoriasis. In a search for new, improved anti-inflammatory therapeutics we have designed a single-domain monoclonal antibody (V(H) H), which recognizes TNF. The antibody component (TNF-V(H) H) is based upon an anti-human TNF Camelidae heavy-chain monoclonal antibody, which was linked to an elastin-like polypeptide (ELP). We demonstrate that ELP fusion to the TNF-V(H) H enhances accumulation of the fusion protein during biomanufacturing in transgenic tobacco plants. With this study, we show for the first time that this plant-derived anti-human TNF-V(H) H antibody was biologically active in vivo. Therefore, therapeutic application of TNF-V(H) H-ELP fusion protein was tested in humanized TNF mice and was shown to be effective in preventing death caused by septic shock. The in vivo persistence of the ELPylated antibody was ∼24 fold longer than that of non-ELPylated TNF-V(H) H.

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Source
http://dx.doi.org/10.1111/j.1467-7652.2010.00523.xDOI Listing

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