Construction of a bispecific single chain antibody for recruitment of cytotoxic T cells to the tumour stroma associated antigen fibroblast activation protein

J Biotechnol. 2001 Dec 28;92(2):159-68. doi: 10.1016/s0168-1656(01)00355-8.

Abstract

Bispecific antibodies directed against tumour associated antigens and the T cell receptor component CD3 for recruitment and tumour targeted activation of T cells represent a novel class of highly specific immunotherapeutics for cancer. We here describe the construction, eukaryotic expression and in vitro functional activity of a new T cell activating bispecific reagent, termed TTS for T cell targeting to the tumour stroma, comprised of a CD3 specific single chain antibody derivative (scFv) fused C-terminally to a 'fibroblast activation protein' (FAP) specific scFv that targets cytotoxic effector cells to FAP. FAP is highly expressed in the vascularised tumoural stroma of most lung, breast and colon carcinomas. It thus represents a selectively tumour associated, yet common marker of many solid tumours and is a potentially ideal candidate marker for efficient targeting of immune effector cells.

MeSH terms

  • Animals
  • Antibodies, Bispecific / biosynthesis*
  • Antibodies, Bispecific / genetics
  • Antibodies, Bispecific / therapeutic use
  • Antigens, Neoplasm*
  • Base Sequence
  • Biomarkers, Tumor*
  • Biotechnology
  • CD3 Complex
  • CHO Cells
  • Cell Line
  • Cloning, Molecular
  • Cricetinae
  • DNA, Recombinant / genetics
  • Endopeptidases
  • Gelatinases
  • Genetic Vectors
  • Growth Substances / immunology*
  • Humans
  • Immunotherapy
  • In Vitro Techniques
  • Lymphocyte Activation
  • Membrane Proteins
  • Neoplasms / immunology*
  • Neoplasms / therapy*
  • Serine Endopeptidases / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured

Substances

  • Antibodies, Bispecific
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CD3 Complex
  • DNA, Recombinant
  • Growth Substances
  • Membrane Proteins
  • Endopeptidases
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • Gelatinases