Nanotheranostics 2020; 4(2):71-82. doi:10.7150/ntno.32876

Research Paper

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

Julie T-W. Wang1*✉, Naomi O. Hodgins1*, Wafa' T. Al-Jamal2, John Maher1, Jane K. Sosabowski3, Khuloud T. Al-Jamal1✉

1. School of Cancer and Pharmaceutical Sciences, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, United Kingdom
2. School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, United Kingdom
3. Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, United Kingdom
* Equal contribution

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Citation:
Wang JTW, Hodgins NO, Al-Jamal WT, Maher J, Sosabowski JK, Al-Jamal KT. Organ Biodistribution of Radiolabelled γδ T Cells Following Liposomal Alendronate Administration in Different Mouse Tumour Models. Nanotheranostics 2020; 4(2):71-82. doi:10.7150/ntno.32876. Available from http://www.ntno.org/v04p0071.htm

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Abstract

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.

Keywords: bisphosphonates, γδ T cells, liposomes, adoptive immunotherapy, nitrogen-containing bisphosphonates