In vitro potency, in vitro and in vivo efficacy of liposomal alendronate in combination with γδ T cell immunotherapy in mice

Hodgins, Naomi O., Al-Jamal, Wafa T., Wang, Julie T-W., Parente-Pereira, Ana C., Liu, Mao, Maher, John and Al-Jamal, Khuloud T. (2016) In vitro potency, in vitro and in vivo efficacy of liposomal alendronate in combination with γδ T cell immunotherapy in mice. Journal of Controlled Release, 241. 229–241. ISSN 0168-3659

[img]
Preview
PDF (Accepted manuscript) - Submitted Version
Download (825kB) | Preview
[img]
Preview
PDF (published_article) - Published Version
Download (988kB) | Preview

Abstract

Nitrogen-containing bisphosphonate (N-BP), including zoledronic acid (ZOL) and alendronate (ALD), have been proposed as sensitisers in γδ T cell immunotherapy in pre-clinical and clinical studies. Therapeutic efficacy of N-BPs is hampered by their rapid renal excretion and high affinity for bone. Liposomal formulations of N-BP have been proposed to improve accumulation in solid tumours. Liposomal alendronate (L-ALD) has been suggested as a suitable alternative to liposomal ZOL (L-ZOL), due to unexpected mice death experienced in pre-clinical studies with the latter. Only one study so far has proven the therapeutic efficacy of L-ALD, in combination with γδ T cell immunotherapy, after intraperitoneal administration of γδ T cell resulting in delayed growth of ovarian cancer in mice. This study aims to assess the in vitro efficacy of L-ALD, in combination with γδ T cell immunotherapy, in a range of cancerous cell lines, using L-ZOL as a comparator. The therapeutic efficacy was tested in a pseudo-metastatic lung mouse model, following intravenous injection of γδ T cell, L-ALD or the combination. In vivo biocompatibility and organ biodistribution studies of L-BPs were undertaken simultaneously. Higher concentrations of L-ALD (40–60 μM) than L-ZOL (3–10 μM) were required to produce a comparative reduction in cell viability in vitro, when used in combination with γδ T cells. Significant inhibition of tumour growth was observed after treatment with both L-ALD and γδ T cells in pseudo-metastatic lung melanoma tumour-bearing mice after tail vein injection of both treatments, suggesting that therapeutically relevant concentrations of L-ALD and γδ T cell could be achieved in the tumour sites, resulting in significant delay in tumour growth.

Item Type: Article
Additional Information: Published under a Creative Commons Attribution 4.0 International license
Uncontrolled Keywords: bisphosphonates,γδ t cells,liposomes,immunotherapy,sensitiser
Faculty \ School: Faculty of Science > School of Pharmacy
Related URLs:
Depositing User: Pure Connector
Date Deposited: 26 Sep 2016 15:00
Last Modified: 22 Apr 2020 01:46
URI: https://ueaeprints.uea.ac.uk/id/eprint/60588
DOI: 10.1016/j.jconrel.2016.09.023

Actions (login required)

View Item View Item