Genetically engineered antibodies and their application to brain delivery

Sherie L. Morrison, Seung Uon Shin

Research output: Contribution to journalReview article

9 Scopus citations

Abstract

Techniques of genetic engineering and expression have been applied to the production of antibodies in a variety of expression systems. Combinatorial libraries produced in bacteriophage may present an alternative to animal immunization as a source of antigen-binding specificities. Transfectomas which express genetically engineered antibody genes provide one approach to overcoming some of the limitations inherent in classical monoclonal antibodies. Novel antibodies have been produced with a variety of modifications: as chimeric antibodies, as 'humanized' antibodies, with catalytic groups, as bifunctional or fusion proteins and as functional fragments such as Fabs or Fvs. The domain structure of the antibody is favorable to such manipulation; the novel proteins often retain their antibody-derived activity and acquire new properties as well. Chimeric and CDR-grafted antibodies have been effective in immunotherapy, but problems of immunogenicity remain. Careful analysis and comparison of effector functions among immunoglobulin isotypes may be applied to the design of effective therapeutic antibodies. In addition, antibody combining specificities can be joined with non-immunoglobulin sequences thereby providing properties not usually found in antibodies. In particular, antibodies fused with the growth factors insulin-like growth factor(IGF)-1, IGF-2 and transferrin have shown increased uptake into the brain parenchyma. These fusion proteins provide a family of reagents with many potential applications.

Original languageEnglish (US)
Pages (from-to)147-175
Number of pages29
JournalAdvanced Drug Delivery Reviews
Volume15
Issue number1-3
DOIs
StatePublished - Jul 1995
Externally publishedYes

Keywords

  • Antibody-growth factor fusion protein
  • Bifunctional antibody
  • Chimeric antibody
  • Combinatorial library
  • Effector function

ASJC Scopus subject areas

  • Pharmaceutical Science

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