Retargeting of T-cell-receptor gamma/delta+ lymphocytes against tumor cells by bispecific monoclonal antibodies. Induction of cytolytic activity and lymphokine production

Int J Cancer Suppl. 1989:4:53-5. doi: 10.1002/ijc.2910440714.

Abstract

We have recently selected MAbs specific for different molecular forms of the TCR gamma/delta (expressed by distinct cell subsets), able to activate TCR gamma/delta+ cells. Two of these reagents (G1 and A13) were used for the construction of bispecific MAbs in conjunction with a MAb (Mov19) directed to ovarian carcinoma cells, using the hybrid hybridoma technique. The G1-derived bispecific MAb GM33.9 efficiently induced lysis of Mov19+ ovarian carcinoma cell lines (IGROVI and SW626) by G1+ clones in a 4-hr 51Cr-release assay. On the other hand, it was ineffective when Mov19- target cells were used. Comparable results were obtained with the A13-derived AM18.4 bispecific MAb when A13+ clones were used as effector cells. Bispecific MAbs were also able to induce secretion of IL-2 and TNF-alpha by TCR gamma/delta+ clones when Mov19+ target cells were present.

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • Antigens, Neoplasm / immunology*
  • Carcinoma / immunology
  • Cytotoxicity, Immunologic
  • Female
  • Humans
  • Lymphocyte Activation / drug effects
  • Lymphokines / biosynthesis*
  • Ovarian Neoplasms / immunology
  • Receptors, Antigen, T-Cell / physiology*
  • Receptors, Antigen, T-Cell, gamma-delta
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Cells, Cultured / immunology

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Lymphokines
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, gamma-delta
  • Tetradecanoylphorbol Acetate