Human gammadelta T cells as mediators of chimaeric-receptor redirected anti-tumour immunity

Br J Haematol. 2004 Aug;126(4):583-92. doi: 10.1111/j.1365-2141.2004.05077.x.


Human peripheral blood gammadelta T cells (Vgamma9(+) Vdelta2(+)) can be selectively expanded in vivo by the systemic administration of aminobisphosphonates without prior antigen priming. To assess the potential of human gammadelta T cells to serve as effector cells of specific anti-tumour immunity, we expanded peripheral blood-derived gammadelta T cells and transduced them with recombinant retrovirus encoding G(D2)- or CD19-specific chimaeric receptors. Flow cytometric analysis of T cells from four individual donors cultured in the presence of zoledronate at day 14 of culture showed selective enrichment of the gammadelta T cell population (Vgamma9(+) Vdelta2(+) CD3(+) CD4(-) CD8(-)) to 73-96% of total CD3(+) T cells. Retroviral gene transfer resulted in chimaeric receptor surface expression in 73 +/- 12% of the population. Transduced gammadelta T cells efficiently recognized antigen-expressing tumour cell targets, as demonstrated by target-specific upregulation of CD69 and secretion of interferon-alpha. Moreover, transduced gammadelta T cells efficiently and specifically lysed the antigen-expressing tumour targets. They could be efficiently expanded in vitro and maintained in culture for prolonged periods. Zoledronate-activated human gammadelta T cells expressing chimaeric receptors may thus serve as potent and specific anti-tumour effector cells. Their responsiveness to stimulation with aminobisphosphonates may enable the selective re-expansion of adoptively transferred T cells in vivo, permitting long lasting anti-tumour immune control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / immunology
  • Cell Division / drug effects
  • Cell Division / immunology
  • Cytotoxicity, Immunologic
  • Diphosphonates / pharmacology
  • Epitopes, T-Lymphocyte / immunology
  • Humans
  • Imidazoles / pharmacology
  • Immunophenotyping
  • Immunotherapy, Adoptive / methods*
  • Interferon-gamma / biosynthesis
  • Lymphocyte Activation / immunology
  • Neoplasms / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / blood*
  • Retroviridae / genetics
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • Transduction, Genetic
  • Tumor Cells, Cultured
  • Zoledronic Acid


  • Antigens, Neoplasm
  • Diphosphonates
  • Epitopes, T-Lymphocyte
  • Imidazoles
  • Receptors, Antigen, T-Cell, gamma-delta
  • Zoledronic Acid
  • Interferon-gamma