Human TNF cytokine neutralization with a vNAR from Heterodontus francisci shark: a potential therapeutic use

MAbs. 2013 Jan-Feb;5(1):80-5. doi: 10.4161/mabs.22593. Epub 2012 Dec 5.

Abstract

The therapeutic use of single domain antibodies (sdAbs) is a promising new approach because these small antibodies maintain antigen recognition and neutralization capacity, have thermal and chemical stability and have good solubility. In this study, using phage display technology, we isolated a variable domain of a IgNAR (vNAR) from a Heterodontus francisci shark immunized against the recombinant human cytokine TNFα (rhTNFα). One clone T43, which expresses the vNAR protein in the periplasmic space, was isolated from the fourth round of panning. T43 had the capacity to recognize rhTNF and neutralize it in vitro, indicating that T43 has potential as a therapeutic that can be used for diseases in which this pro-inflammatory cytokine needs to be controlled.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Neutralizing / biosynthesis
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / therapeutic use
  • Antibody Specificity
  • Humans
  • Immunization
  • Immunoglobulin Variable Region / biosynthesis
  • Immunoglobulin Variable Region / chemistry
  • Immunoglobulin Variable Region / immunology
  • Immunoglobulins / biosynthesis
  • Immunoglobulins / chemistry
  • Immunoglobulins / immunology
  • Male
  • Mice
  • Molecular Sequence Data
  • Neutralization Tests
  • Peptide Library
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Sharks / immunology*
  • Shock, Septic / immunology
  • Single-Domain Antibodies / biosynthesis
  • Single-Domain Antibodies / chemistry
  • Single-Domain Antibodies / immunology*
  • Single-Domain Antibodies / therapeutic use
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology*

Substances

  • Antibodies, Neutralizing
  • Immunoglobulin Variable Region
  • Immunoglobulins
  • Peptide Library
  • Recombinant Proteins
  • Single-Domain Antibodies
  • Tumor Necrosis Factor-alpha