Cancer Immunology, Immunotherapy

, Volume 56, Issue 8, pp 1285–1297

Chemotherapy and zoledronate sensitize solid tumour cells to Vγ9Vδ2 T cell cytotoxicity

  • Stephen R. Mattarollo
  • Tony Kenna
  • Mie Nieda
  • Andrew J. Nicol
Original Article

DOI: 10.1007/s00262-007-0279-2

Cite this article as:
Mattarollo, S.R., Kenna, T., Nieda, M. et al. Cancer Immunol Immunother (2007) 56: 1285. doi:10.1007/s00262-007-0279-2

Abstract

Combinations of cellular immune-based therapies with chemotherapy and other antitumour agents may be of significant clinical benefit in the treatment of many forms of cancer. Gamma delta (γδ) T cells are of particular interest for use in such combined therapies due to their potent antitumour cytotoxicity and relative ease of generation in vitro. Here, we demonstrate high levels of cytotoxicity against solid tumour-derived cell lines with combination treatment utilizing Vγ9Vδ2 T cells, chemotherapeutic agents and the bisphosphonate, zoledronate. Pre-treatment with low concentrations of chemotherapeutic agents or zoledronate sensitized tumour cells to rapid killing by Vγ9Vδ2 T cells with levels of cytotoxicity approaching 90%. In addition, zoledronate enhanced the chemotherapy-induced sensitization of tumour cells to Vγ9Vδ2 T cell cytotoxicity resulting in almost 100% lysis of tumour targets in some cases. Vγ9Vδ2 T cell cytotoxicity was mediated by perforin following TCR-dependent and isoprenoid-mediated recognition of tumour cells. Production of IFN-γ by Vγ9Vδ2 T cells was also induced after exposure to sensitized targets. We conclude that administration of Vγ9Vδ2 T cells at suitable intervals after chemotherapy and zoledronate may substantially increase antitumour activities in a range of malignancies.

Keywords

γδ T cells Bisphosphonate Chemotherapy Immunotherapy Antitumour Cancer 

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Stephen R. Mattarollo
    • 1
    • 4
  • Tony Kenna
    • 2
  • Mie Nieda
    • 3
  • Andrew J. Nicol
    • 1
  1. 1.Centre for Immune and Targeted TherapyUniversity of QueenslandBrisbaneAustralia
  2. 2.Centre for Immunology and Cancer ResearchUniversity of QueenslandBrisbaneAustralia
  3. 3.Medinet Medical InstituteTokyoJapan
  4. 4.Centre for Immune and Targeted TherapyGreenslopes Private HospitalBrisbaneAustralia

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