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

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

Engineering hepatitis B virus core particles for targeting HER2 receptors in vitro and in vivo

We acknowledge funding from Biotechnology and Biological Sciences Research Council (BBSRC; (BB/J008656/1)) and the EU FP7-ITN Marie-Curie Network programme RADDEL (290023). NH is a recipient of Graduate School King's Health Partner's scholarship. RK is a Marie-Curie Fellow. S.B. acknowledges funding from the European Research Council under the 7th Framework Program (FP7), ERC Starting Grant No. 335078 COLOURATOMS, and the Integrated Infrastructure Initiative No. 262348European Soft Matter Infrastructure, ESM