A fully human CD19/CD3 bi-specific antibody triggers potent and specific cytotoxicity by unstimulated T lymphocytes against non-Hodgkin's lymphoma

Biotechnol Lett. 2012 Jul;34(7):1183-91. doi: 10.1007/s10529-012-0895-6. Epub 2012 Mar 16.

Abstract

The use of a bi-specific antibody (BsAb) is an attractive and specific approach to cancer therapy. We have constructed a fully human recombinant single chain Fv BsAb against CD19 and CD3 that was an effective treatment in an animal model of non-Hodgkin's lymphoma (NHL). The CD19/CD3 BsAb was expressed in CHO cells and purified by Ni-column chromatography. Flow cytometry revealed that the CD19/CD3 BsAb specifically bound to both CD19 and CD3-positive cells. In vitro, the CD19/CD3 BsAb could stimulate T cell proliferation and induce the lysis of cultured Raji cells in the presence of unstimulated T lymphocytes. In vivo, the CD19/CD3 BsAb efficiently inhibited tumour growth in SCID mice of NHL, and the survival time of the mice was significantly prolonged. Therefore, our CD19/CD3 BsAb is a useful tool that could be a suitable candidate for treatment of NHL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bispecific / genetics
  • Antibodies, Bispecific / immunology*
  • Antibodies, Bispecific / therapeutic use
  • Antigens, CD19 / immunology*
  • CD3 Complex / immunology*
  • CHO Cells
  • Cell Proliferation
  • Chromatography, Affinity
  • Cricetinae
  • Disease Models, Animal
  • Humans
  • Immunotherapy / methods
  • Lymphoma, Non-Hodgkin / immunology*
  • Mice
  • Mice, SCID
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Recombinant Proteins / therapeutic use
  • T-Lymphocytes, Cytotoxic / immunology*
  • Treatment Outcome

Substances

  • Antibodies, Bispecific
  • Antigens, CD19
  • CD3 Complex
  • Recombinant Proteins