Induction of cytotoxic T lymphocytes by CEA peptide-pulsed γδ T-cells isolated from patients with advanced cancer

Anticancer Res. 2011 Jul;31(7):2419-24.

Abstract

Cytotoxic γδ T-cells recognize antigens directly without the need for antigen processing and presentation. Recently, it was reported that they can also present antigens and proliferate in vitro. In this study, we examined whether γδ T-cells isolated from patients with advanced cancer can be used for immunotherapy. Twenty-two inoperable patients with multiple cancer metastases were enrolled in the study. There was no significant difference in the ratio of γδ T-cells within the peripheral blood mononuclear cell population isolated from healthy volunteers and cancer patients. γδ T-Cells isolated from cancer patients were expanded 2- to 5-fold using zoledronic acid or 2-methyl-3butenyl-1-pyrophosphate and IL-2. Autologous CD8(+) T-cells co-cultured with expanded CEA peptide-pulsed γδ T-cells from cancer patients with HLA-A24 killed more CEA-positive HLA-A24-matched gastric cancer cells and secreted higher levels of interferon-γ. These results suggest that γδ T-cells from cancer patients may be ideal candidates for adoptive immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigen Presentation
  • Carcinoembryonic Antigen / immunology*
  • Cell Separation
  • Cells, Cultured / drug effects
  • Cells, Cultured / immunology
  • Diphosphonates / pharmacology
  • Female
  • HLA-A Antigens / immunology
  • HLA-A24 Antigen
  • Humans
  • Imidazoles / pharmacology
  • Immunotherapy, Adoptive*
  • Interferon-gamma / metabolism
  • Interleukin-2 / pharmacology
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Neoplasms / blood
  • Neoplasms / immunology*
  • Organophosphorus Compounds / pharmacology
  • Receptors, Antigen, T-Cell, gamma-delta / analysis
  • Stomach Neoplasms / pathology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology*
  • Zoledronic Acid

Substances

  • 2-methyl-3-butenyl-1-pyrophosphate
  • Carcinoembryonic Antigen
  • Diphosphonates
  • HLA-A Antigens
  • HLA-A24 Antigen
  • Imidazoles
  • Interleukin-2
  • Organophosphorus Compounds
  • Receptors, Antigen, T-Cell, gamma-delta
  • Zoledronic Acid
  • Interferon-gamma