Generation of a rabbit V(H) domain antibody polyspecific to c-Met and adenoviral knob protein

Biochem Biophys Res Commun. 2006 Jan 6;339(1):305-12. doi: 10.1016/j.bbrc.2005.10.208. Epub 2005 Nov 15.


Several types of bispecific antibodies with affinity to both adenoviral coat proteins and a targeted antigen have been developed with the aim of providing the specific delivery of adenoviral gene therapy vehicle. From a phage display library of combinatorial dAb2s (each with an anti-adenoviral knob protein V(H) fragment linked with an anti-c-Met V(H)), we serendipitously enriched and isolated a clone, JS5, that has polyspecificity such that it binds both the adenoviral knob protein and c-Met, despite having only one V(H) domain. Our indirect observations suggest that the polyspecificity of JS5 is developed through accumulation of antibody specificity. The method of sequential immunization of a rabbit, first with the adenoviral knob protein and then with target antigens, may provide a method by which monoclonal antibodies with stand-alone polyspecificity may be developed. Such targeted polyspecific antibodies could readily be used for re-directing adenoviral vectors to target cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / immunology*
  • Amino Acid Sequence
  • Animals
  • Antibodies, Bispecific*
  • Humans
  • Immunoglobulin Heavy Chains / immunology*
  • Immunoglobulin Variable Region / immunology*
  • Molecular Sequence Data
  • Peptide Library
  • Proto-Oncogene Proteins c-met / immunology*
  • Rabbits
  • Viral Proteins / immunology*


  • Antibodies, Bispecific
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Peptide Library
  • Viral Proteins
  • Proto-Oncogene Proteins c-met