School of Cancer and Pharmaceutical Sciences, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, United Kingdom.
School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, United Kingdom.
Nanotheranostics. 2020 Feb 6;4(2):71-82. doi: 10.7150/ntno.32876. eCollection 2020.
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.
γδ T 细胞免疫疗法已被证明在临床前和临床研究中均能有效延缓肿瘤生长。人们已经指出,细胞在肿瘤内聚集的能力以及与过继性 T 细胞转移的临床研究疗效之间的关联非常重要。我们之前曾报道过,局部或全身注射 γδ T 细胞后,阿仑膦酸脂质体(L-ALD)增加了用卵巢癌、黑色素瘤、胰腺癌或实验性肺转移瘤模型接种的小鼠的这种治疗的疗效。本研究旨在检查在预先用 L-ALD 注射的荷黑色素瘤细胞系 A375Pβ6.luc 的 NOD-SCID gamma(NSG)小鼠的皮下(SC)、腹腔(IP)或实验性转移性肺肿瘤中,人 γδ T 细胞的器官生物分布和肿瘤摄取情况。总的来说,在不同的肿瘤模型中,γδ T 细胞的血液特征和器官生物分布变化很小。例外的是,预先用 L-ALD 注射的 IP 肿瘤和实验性转移性肺肿瘤荷瘤小鼠的肝脏积聚显著减少,分别在肺部和肿瘤肺部的 γδ T 细胞摄取量最高。在 SC 和 IP 肿瘤中发现的 γδ T 细胞计数较低。