Abstract
Background aims
Adoptive immunotherapy is emerging as a potent anti-tumor treatment modality; Vγ9Vδ2
T cells may represent appropriate agents for such cancer immunotherapy. To improve
the currently limited success of Vγ9Vδ2 T-cell–based immunotherapy, we examined the
in vivo dynamics of these adoptively-transferred cells and hypothesized that interleukin
(IL)-15 is the potential factor for Vγ9δ2 T cell in vivo survival.
Methods
We conducted a clinical trial of adoptive Vγ9Vδ2 T-cell transfer therapy in six colorectal
cancer patients who received pulmonary metastasectomy. Patients' peripheral blood
mononuclear cells were stimulated with zoledronate (5 μmol/L) and IL-2 (1000 IU/mL)
for 14 d. Harvested cells, mostly Vγ9Vδ2 T cells, were given intravenously weekly
without additional IL-2 eight times in total. The frequency, phenotype and common
γ-chain cytokine receptor expression of Vγ9Vδ2 T cells in peripheral blood was monitored
by flow cytometry at each time point during treatment and 4 and 12 weeks after the
last administration.
Results
Adoptively transferred Vγ9Vδ2 T cells expanded well without exogenous IL-2 administration
or lymphodepleting preconditioning. They maintained effector functions in terms of
interferon-γ secretion and prompt release of cytotoxic granules in response to PMA/ionomycin
or isopentenyl pyrophosphate–positive cells. Because they are IL-2Rα−IL-7Rα−IL-15Rα−IL-2Rβ+γc+, it is likely that IL-2 or IL-15 is required for their maintenance.
Conclusions
The persistence of large numbers of functionally active adoptively transferred Vγ9Vδ2
T cells in the absence of exogenous IL-2 implies that an endogenous factor, such as
IL-15 transpresentation, is adequate to support these cells in vivo.
Key Words
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Article info
Publication history
Published online: February 07, 2013
Accepted:
December 18,
2012
Received:
August 23,
2012
Identification
Copyright
© 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
