Chemotherapy and zoledronate sensitize solid tumour cells to V γ9Vδ2T cell cytotoxicity

Mattarollo, Stephen R., Kenna, Tony, Nieda, Mie and Nicol, Andrew J. (2007) Chemotherapy and zoledronate sensitize solid tumour cells to V γ9Vδ2T cell cytotoxicity. Cancer Immunology Immunotherapy, 56 8: 1285-1297. doi:10.1007/s00262-007-0279-2


Author Mattarollo, Stephen R.
Kenna, Tony
Nieda, Mie
Nicol, Andrew J.
Title Chemotherapy and zoledronate sensitize solid tumour cells to V γ9Vδ2T cell cytotoxicity
Journal name Cancer Immunology Immunotherapy   Check publisher's open access policy
ISSN 0340-7004
Publication date 2007-01-01
Sub-type Article (original research)
DOI 10.1007/s00262-007-0279-2
Volume 56
Issue 8
Start page 1285
End page 1297
Total pages 13
Place of publication New York
Publisher Springer
Collection year 2008
Language eng
Subject C1
320206 Tumor Immunology
730108 Cancer and related disorders
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 (gamma delta) 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 V gamma 9V delta 2 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 V gamma 9V delta 2 T cells with levels of cytotoxicity approaching 90%. In addition, zoledronate enhanced the chemotherapy-induced sensitization of tumour cells to V gamma 9V delta 2 T cell cytotoxicity resulting in almost 100% lysis of tumour targets in some cases. V gamma 9V delta 2 T cell cytotoxicity was mediated by perforin following TCR-dependent and isoprenoid-mediated recognition of tumour cells. Production of IFN-gamma by V gamma 9V delta 2 T cells was also induced after exposure to sensitized targets. We conclude that administration of V gamma 9V delta 2 T cells at suitable intervals after chemotherapy and zoledronate may substantially increase antitumour activities in a range of malignancies.
Keyword Oncology
Immunology
Gamma Delta T Cells
Bisphosphonate
Chemotherapy
Immunotherapy
Antitumour
Cancer
Prostate-cancer Cells
In-vitro
Mediated Cytotoxicity
Ex-vivo
3rd-generation Bisphosphonate
Nonpeptide Antigens
Monoclonal-antibody
Multiple-myeloma
Bone Metastases
Breast-cancer
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2008 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Tue, 19 Feb 2008, 03:13:07 EST