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

ABSTRACT: Nitrogen-containing bisphosphonates (N-BP), including zoledronic acid (ZOL) and alendronate (ALD), have been proposed as sensitisers in ?? 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 ALD (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 ?? T cell immunotherapy, after intraperitoneal administration of ?? 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 ?? 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 ?? T cell, L-ALD or the combination. In vivo biocompatibility and organ biodistribution studies of L-N-BPs were undertaken simultaneously. Higher concentrations of L-ALD (40-60?M) than L-ZOL (3-10?M) were required to produce a comparative reduction in cell viability in vitro, when used in combination with ?? T cells. Significant inhibition of tumour growth was observed after treatment with both L-ALD and ?? 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 ?? T cell could be achieved in the tumour sites, resulting in significant delay in tumour growth.

SUBMITTER: Hodgins NO

PROVIDER: S-EPMC5073077 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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

Hodgins Naomi O NO Al-Jamal Wafa' T WT Wang Julie T-W JT Parente-Pereira Ana C AC Liu Mao M Maher John J Al-Jamal Khuloud T KT

Journal of controlled release : official journal of the Controlled Release Society 20160921

Nitrogen-containing bisphosphonates (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 ALD (L-ALD) has been suggested as a suitable alternative to liposomal ZOL (L-ZOL), due to unexpecte ...[more]

PMID: 27664328

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Dataset Information

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

Publications

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

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