TY - JOUR
T1 - In Vivo PET Tracking of 89Zr-Labeled Vγ9Vδ2 T Cells to Mouse Xenograft Breast Tumors Activated with Liposomal Alendronate
AU - Man, Francis
AU - Lim, Lindsay
AU - Volpe, Alessia
AU - Gabizon, Alberto
AU - Shmeeda, Hilary
AU - Draper, Benjamin
AU - Parente-Pereira, Ana C.
AU - Maher, John
AU - Blower, Philip J.
AU - Fruhwirth, Gilbert O.
AU - T.M. de Rosales, Rafael
N1 - Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2019/1/2
Y1 - 2019/1/2
N2 - Gammadelta T (γδ-T) cells are strong candidates for adoptive immunotherapy in oncology due to their cytotoxicity, ease of expansion and favorable safety profile. The development of γδ-T-cell therapies would benefit from non-invasive cell tracking methods and increased targeting to tumor sites. Here we report the use of [89Zr]Zr(oxinate)4 to track Vγ9Vδ2 T cells in vivo by positron emission tomography (PET). In vitro, we showed that 89Zr-labeled Vγ9Vδ2 T cells retained their viability, proliferative capacity and anti-cancer cytotoxicity with minimal DNA damage for amounts of 89Zr ≤20 mBq/cell. Using a mouse xenograft model of human breast cancer, 89Zr-labeled γδ T cells were tracked by PET imaging over 1 week. To increase tumor antigen expression, the mice were pre-treated with PEGylated liposomal alendronate. Liposomal alendronate, but not placebo liposomes or non-liposomal alendronate, significantly increased the 89Zr signal in the tumors, suggesting increased homing of γδ-T cells to the tumors. γδ-T-cell trafficking to tumors occurred within 48 h of administration. The presence of γδ-T cells in tumors, liver and spleen was confirmed by histology. Our results demonstrate the suitability of [89Zr]Zr(oxinate)4 as a cell labeling agent for therapeutic T cells and the potential benefits of liposomal bisphosphonate treatment before γδ-T cell administration.
AB - Gammadelta T (γδ-T) cells are strong candidates for adoptive immunotherapy in oncology due to their cytotoxicity, ease of expansion and favorable safety profile. The development of γδ-T-cell therapies would benefit from non-invasive cell tracking methods and increased targeting to tumor sites. Here we report the use of [89Zr]Zr(oxinate)4 to track Vγ9Vδ2 T cells in vivo by positron emission tomography (PET). In vitro, we showed that 89Zr-labeled Vγ9Vδ2 T cells retained their viability, proliferative capacity and anti-cancer cytotoxicity with minimal DNA damage for amounts of 89Zr ≤20 mBq/cell. Using a mouse xenograft model of human breast cancer, 89Zr-labeled γδ T cells were tracked by PET imaging over 1 week. To increase tumor antigen expression, the mice were pre-treated with PEGylated liposomal alendronate. Liposomal alendronate, but not placebo liposomes or non-liposomal alendronate, significantly increased the 89Zr signal in the tumors, suggesting increased homing of γδ-T cells to the tumors. γδ-T-cell trafficking to tumors occurred within 48 h of administration. The presence of γδ-T cells in tumors, liver and spleen was confirmed by histology. Our results demonstrate the suitability of [89Zr]Zr(oxinate)4 as a cell labeling agent for therapeutic T cells and the potential benefits of liposomal bisphosphonate treatment before γδ-T cell administration.
KW - bisphosphonate
KW - cancer immunotherapy
KW - cell immunotherapy
KW - cell tracking
KW - liposome
KW - nanomedicine
KW - PET
KW - zirconium-89
UR - http://www.scopus.com/inward/record.url?scp=85056272403&partnerID=8YFLogxK
U2 - 10.1016/j.ymthe.2018.10.006
DO - 10.1016/j.ymthe.2018.10.006
M3 - Article
C2 - 30429045
AN - SCOPUS:85056272403
SN - 1525-0016
VL - 27
SP - 219
EP - 229
JO - Molecular therapy : the journal of the American Society of Gene Therapy
JF - Molecular therapy : the journal of the American Society of Gene Therapy
IS - 1
ER -
