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

Mattarollo, Stephen R., Kenna, Tony, Nieda, Mie, & Nicol, Andrew J. (2007) Chemotherapy and zoledronate sensitize solid tumour cells to Vγ9Vδ2 T cell cytotoxicity. Cancer Immunology, Immunotherapy, 56(8), pp. 1285-1297.

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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.

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ID Code: 94068
Item Type: Journal Article
Refereed: Yes
Keywords: γδ T cells, Antitumour, Bisphosphonate, Cancer, Chemotherapy, Immunotherapy, antineoplastic agent, cisplatin, doxorubicin, etoposide, gamma interferon, perforin, vincristine, zoledronic acid, antineoplastic activity, article, cancer combination chemotherapy, cancer immunotherapy, cellular immunity, concentration response, controlled study, cytotoxic T lymphocyte, drug potency, drug targeting, human, human cell, molecular recognition, priority journal, sensitization, solid tumor, T lymphocyte, Adenocarcinoma, Antineoplastic Agents, Apoptosis, Breast Neoplasms, Burkitt Lymphoma, Carcinoma, Cell Line, Tumor, Colorectal Neoplasms, Concanavalin A, Cytotoxicity, Immunologic, Diphosphonates, Drug Screening Assays, Antitumor, Drug Synergism, Female, Genes, T-Cell Receptor delta, Genes, T-Cell Receptor gamma, Humans, Imidazoles, Interferon Type II, Lovastatin, Lung Neoplasms, Male, Membrane Glycoproteins, Neoplasms, Pore Forming Cytotoxic Proteins, Prostatic Neoplasms, Receptors, Antigen, T-Cell, gamma-delta, T-Lymphocyte Subsets, Urinary Bladder Neoplasms
DOI: 10.1007/s00262-007-0279-2
ISSN: 0340-7004
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2007 Springer-Verlag
Deposited On: 22 Mar 2016 05:31
Last Modified: 23 Mar 2016 04:11

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