In Vivo PET Tracking of 89Zr-Labeled Vγ9Vδ2 T Cells to Mouse Xenograft Breast Tumors Activated with Liposomal Alendronate

Man, Francis; Lim, Lindsay; Volpe, Alessia; Gabizón, Alberto; Shmeeda, Hilary; Draper, Benjamin; Parente-Pereira, Ana C.; Maher, John; Blower, Philip J.; Fruhwirth, Gilbert O.; Rosales, Rafael T. M. de

doi:10.1016/j.ymthe.2018.10.006

Cited by 95 publications

(130 citation statements)

References 51 publications

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“…Only few studies, however, have addressed the fate of adoptively transferred Vγ9Vδ2 T cells in mice. Although tracing studies suggest in vivo cell survival for periods of at least one to two weeks upon adoptive transfer [146,147], the functional activity of Vγ9Vδ2 T cells re-isolated from tumor bearing mice had vanished over time [147]. Hence, the requirement for high numbers and repetitive administration of human γδ T cells in these models may-at least in part-be ascribed to their limited persistence and functional activity in murine hosts [147].…”

Section: Preclinical Modelingmentioning

confidence: 99%

Vγ9Vδ2 T Cells: Can We Re-Purpose a Potent Anti-Infection Mechanism for Cancer Therapy?

Künkele

Wesch

Oberg

et al. 2020

Cells

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Cancer therapies based on in vivo stimulation, or on adoptive T cell transfer of Vγ9Vδ2 T cells, have been tested in the past decades but have failed to provide consistent clinical efficacy. New, promising concepts such as γδ Chimeric Antigen Receptor (CAR) -T cells and γδ T-cell engagers are currently under preclinical evaluation. Since the impact of factors, such as the relatively low abundance of γδ T cells within tumor tissue is still under investigation, it remains to be shown whether these effector T cells can provide significant efficacy against solid tumors. Here, we highlight key learnings from the natural role of Vγ9Vδ2 T cells in the elimination of host cells bearing intracellular bacterial agents and we translate these into the setting of tumor therapy. We discuss the availability and relevance of preclinical models as well as currently available tools and knowledge from a drug development perspective. Finally, we compare advantages and disadvantages of existing therapeutic concepts and propose a role for Vγ9Vδ2 T cells in immune-oncology next to Cluster of Differentiation (CD) 3 activating therapies.

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Section: Preclinical Modelingmentioning

confidence: 99%

Vγ9Vδ2 T Cells: Can We Re-Purpose a Potent Anti-Infection Mechanism for Cancer Therapy?

Künkele

Wesch

Oberg

et al. 2020

Cells

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“…Aside from the present study on umbilical cord tissue-derived MSCs, 89 Zr-oxine-labelling and PET imaging has also been demonstrated with T-cells, dendritic cells, and bone marrow cells [12, 13, 17, 19]. Together, these studies illustrate the benefits of 89 Zr-oxine labelling: fast implementation, non-invasive tracking over a week post-injection, and interpretation of images un-complicated by the degree of background signal given by the systemically-administered tracers used with nuclear reporter-gene systems [36].…”

Section: Discussionmentioning

confidence: 89%

“…With the introduction of total-body clinical PET scanners this is set to increase by a further ∼40-fold, reducing scan times and radioactive doses for patients and thus increasing the practicality of whole-body cell tracking in the clinic [15]. A handful of preclinical studies have so far shown the worth of 89 Zr-oxine in tracking cell therapies in mouse models, including T-cells [16, 17], dendritic cells, NK cells [13], and bone marrow cells [18, 19]. However 89 Zr-oxine toxicity is dose-dependent and varies between cell types, requiring individual evaluation with each prospective cell therapy prior to clinical implementation.…”

Section: Introductionmentioning

confidence: 99%

⁸⁹Zr-oxine labelling and PET imaging shows lung delivery of a cell/gene cancer therapy

Patrick

Kolluri

Thin

et al. 2019

Preprint

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PurposeMSCTRAIL is a new stem cell-based therapy for lung cancer, currently in phase I evaluation (ClinicalTrials.gov ref: NCT03298763). Biodistribution of cell therapies is rarely assessed in clinical trials, despite cell delivery to the target site often being critical to presumed mechanism of action. This preclinical study demonstrates that MSCTRAIL biodistribution dynamics can be detected non-invasively using 89Zr-oxine labelling and PET imaging, thus supporting use of this cell tracking technology in phase II evaluation.MethodsMSCTRAIL were radiolabelled with a range of 89Zr-oxine doses, and assayed for cell viability, phenotype and therapeutic efficacy post-labelling. Cell biodistribution was imaged in a mouse model of lung cancer using PET imaging and bioluminescence imaging (BLI) to confirm cell viability and location in vivo up to 1 week post-injection.ResultsMSCTRAIL retained therapeutic efficacy and MSC phenotype at doses up to and above those required for clinical imaging. The effect of 89Zr-oxine labelling on cell proliferation rate was dose and time-dependent. PET imaging showed delivery of MSCTRAIL to the lungs in a mouse model of lung cancer, with PET signal correlating with the presence of viable cells as assessed by bioluminescence imaging, ex vivo autoradiography and matched fluorescence imaging on lung tissue sections. Human dosimetry estimates were produced using simulations and preclinical biodistribution data.Conclusion89Zr-oxine labelling and PET imaging present an attractive method of evaluating the biodistribution of new cell-therapies, such as MSCTRAIL. This offers to improve understanding of mechanism of action, migration dynamics and interpatient variability of MSCTRAIL and other cell-based therapies.

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“…Uptake of human γδ T cells in mice has been mostly examined qualitatively in tumours and other organs such as lymph nodes and spleen by immunohistochemical analysis [7,10,22,23]. Quantitative assessments on whole body and tumour biodistribution of γδ T cells have been studied in syngeneic [24] or xenograft [23] tumour models injecting murine or human γδ T cells, respectively. This work aims to quantitatively compare, and for the first time, the biodistribution profiles of human γδ T cells in immune-compromised mice, implanted with human melanoma A375 Pβ6 tumours at three different locations: subcutaneous (SC), intraperitoneal (IP) or experimental metastatic lung tumours.…”

Section: Ivyspringmentioning

confidence: 99%

Organ Biodistribution of Radiolabelled γδ T Cells Following Liposomal Alendronate Administration in Different Mouse Tumour Models

Wang¹,

Hodgins²,

Al-Jamal³

et al. 2020

Nanotheranostics

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Vγ9Vδ2 T cell immunotherapy has been shown to be effective in delaying tumour growth in both pre-clinical and clinical studies. It has been pointed out the importance of the ability of cells to accumulate within tumours and the association with therapeutic efficacy in clinical studies of adoptive T cell transfer. We have previously reported that alendronate liposomes (L-ALD) increase the efficacy of this therapy after localised or systemic injection of γδ T cells in mice, inoculated with ovarian, melanoma, pancreatic or experimental lung metastasis tumour models, respectively. This study aimed to examine the organ biodistribution and tumour uptake of human γδ T cells in subcutaneous (SC), intraperitoneal (IP) or experimental metastatic lung tumours, established in NOD-SCID gamma (NSG) mice using the melanoma cell line A375Pβ6.luc. pre-injected with L-ALD. Overall, small variations in blood profiles and organ biodistribution of γδ T cells among the different tumour models were observed. Exceptionally, IP-tumour and experimental metastatic lung-tumour bearing mice pre-injected with L-ALD showed a significant decrease in liver accumulation, and highest uptake of γδ T cells in lungs and tumour-bearing lungs, respectively. Lower γδ T cell count was found in the SC and IP tumours.

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In Vivo PET Tracking of 89Zr-Labeled Vγ9Vδ2 T Cells to Mouse Xenograft Breast Tumors Activated with Liposomal Alendronate

Cited by 95 publications

References 51 publications

Vγ9Vδ2 T Cells: Can We Re-Purpose a Potent Anti-Infection Mechanism for Cancer Therapy?

Vγ9Vδ2 T Cells: Can We Re-Purpose a Potent Anti-Infection Mechanism for Cancer Therapy?

⁸⁹Zr-oxine labelling and PET imaging shows lung delivery of a cell/gene cancer therapy

Organ Biodistribution of Radiolabelled γδ T Cells Following Liposomal Alendronate Administration in Different Mouse Tumour Models

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In Vivo PET Tracking of 89Zr-Labeled Vγ9Vδ2 T Cells to Mouse Xenograft Breast Tumors Activated with Liposomal Alendronate

Cited by 95 publications

References 51 publications

Vγ9Vδ2 T Cells: Can We Re-Purpose a Potent Anti-Infection Mechanism for Cancer Therapy?

Vγ9Vδ2 T Cells: Can We Re-Purpose a Potent Anti-Infection Mechanism for Cancer Therapy?

89Zr-oxine labelling and PET imaging shows lung delivery of a cell/gene cancer therapy

Organ Biodistribution of Radiolabelled γδ T Cells Following Liposomal Alendronate Administration in Different Mouse Tumour Models

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⁸⁹Zr-oxine labelling and PET imaging shows lung delivery of a cell/gene cancer therapy