Clinical evaluation of autologous gamma delta T cell-based immunotherapy for metastatic solid tumours

Nicol, A. J., Tokuyama, H., Mattarollo, S. R., Hagi, T., Suzuki, K., Yokokawa, K. and Nieda, M. (2011) Clinical evaluation of autologous gamma delta T cell-based immunotherapy for metastatic solid tumours. British Journal of Cancer, 105 6: 778-786. doi:10.1038/bjc.2011.293


Author Nicol, A. J.
Tokuyama, H.
Mattarollo, S. R.
Hagi, T.
Suzuki, K.
Yokokawa, K.
Nieda, M.
Title Clinical evaluation of autologous gamma delta T cell-based immunotherapy for metastatic solid tumours
Formatted title
Clinical evaluation of autologous gamma delta T cell-based immunotherapy for metastatic solid tumours
Journal name British Journal of Cancer   Check publisher's open access policy
ISSN 0007-0920
1532-1827
Publication date 2011-09-06
Sub-type Article (original research)
DOI 10.1038/bjc.2011.293
Open Access Status DOI
Volume 105
Issue 6
Start page 778
End page 786
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2012
Language eng
Formatted abstract
Background: Adoptive transfer of ex vivo expanded autologous Vγ9Vδ2 T cells may be of therapeutic benefit for cancer because of their potent direct cytotoxicity towards tumour cells, synergistic cytotoxicity when combined with aminobisphosphonates and enhancement of antibody-dependent cell-mediated cytotoxicity.

Methods: To determine the feasibility and clinical safety of therapy with ex vivo expanded, activated Vγ9Vδ2 T cells in combination with zoledronate, we enrolled 18 subjects with advanced solid tumours into a phase I clinical study. Administered indium111-oxine-labelled Vγ9Vδ2 T cells were tracked in a cohort of patients.

Results: Administered Vγ9Vδ2 T cells had an activated effector memory phenotype, expressed chemokine receptors predictive of homing to peripheral tissues and were cytotoxic in vitro against tumour targets. Adoptively transferred Vγ9Vδ2 T cells trafficked predominantly to the lungs, liver and spleen and, in some patients, to metastatic tumour sites outside these organs. No dose-limiting toxicity was observed, but most patients progressed on study therapy. However, three patients administered Vγ9Vδ2 T cells while continuing previously ineffective therapy had disease responses, suggesting an additive effect.

Conclusion: Therapy with aminobisphosphonate-activated Vγ9Vδ2 T cells is feasible and well tolerated, but therapeutic benefits appear only likely when used in combination with other therapies.
Keyword Gamma delta T cells
V gamma 9V delta 2 T cells
Immunotherapy
Clinical trial
Ex-vivo expansion
Adoptive immunotherapy
Mediated recognition
Nonpeptide antigens
Peripheral-blood
Prostate-cancer
Lymphocytes-T
In-vitro
Zoledronate
Immunity
Vγ9Vδ2 T cells
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
 
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