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

• Published in: Nanotheranostics (Sydney, NSW) Vol. 4; no. 2; pp. 71 - 82
• Main Authors: Wang, Julie T-W, Hodgins, Naomi O, Al-Jamal, Wafa' T, Maher, John, Sosabowski, Jane K, Al-Jamal, Khuloud T
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher 2020
• Subjects: Alendronate - administration & dosage; Alendronate - pharmacokinetics; Animals; Cells, Cultured; Humans; Immunotherapy, Adoptive - methods; Intraepithelial Lymphocytes - cytology; Intraepithelial Lymphocytes - metabolism; Liposomes - administration & dosage; Liposomes - pharmacokinetics; Male; Mice; Mice, Inbred NOD; Mice, SCID; Research Paper; Tissue Distribution; nitrogen-containing bisphosphonates; γδ T cells; bisphosphonates; liposomes; adoptive immunotherapy
• DOI: 10.7150/ntno.32876
• ISSN: 2206-7418

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.