Bispecific antibodies increase T-cell stimulatory capacity in vitro of human autologous virus-modified tumor vaccine

Clin Cancer Res. 1998 Mar;4(3):721-30.

Abstract

The production and functional testing of two new bispecific (bs) hybrid antibodies [Abs; bs Ab hemagglutinin-neuraminidase (HN) x CD3 and bs Ab HN x CD28] designed for cancer vaccine modification are described. They allow distinct modifications of the human tumor cell vaccine ATV-NDV, an autologous tumor cell vaccine already modified by infection with Newcastle disease virus. The bs Abs use the viral HN molecule as a common foreign anchoring molecule for attachment to the tumor cells and allow the introduction of anti-CD3 or anti-CD28 T-cell-stimulatory molecules. The bs Abs attached to tumor target cells were able to cross-link CTL effector cells and up-regulate T-cell activation markers on autologous cancer patient-derived CD4 and CD8 T lymphocytes. This strategy of combining a cellular vaccine with a bs Ab is highly specific, quick, and economical and has broad-range applications. Five ng or less of target cell-bound bs Ab HN x CD28 were effective at augmenting T-cell-mediated antitumor cytotoxicity.

MeSH terms

  • Antibodies, Bispecific / pharmacology*
  • Antigens, CD / analysis
  • CD28 Antigens / immunology*
  • CD3 Complex / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines*
  • Cell Line
  • Colonic Neoplasms
  • Gamma Rays
  • HN Protein / immunology*
  • Humans
  • Hybridomas
  • Immunophenotyping
  • Immunotherapy / methods
  • Jurkat Cells
  • Lymphocyte Activation
  • Newcastle disease virus*
  • T-Lymphocytes / immunology*
  • Tumor Cells, Cultured

Substances

  • Antibodies, Bispecific
  • Antigens, CD
  • CD28 Antigens
  • CD3 Complex
  • Cancer Vaccines
  • HN Protein