Non-viral immune electro-gene therapy induces potent anti-tumour responses and has a curative effect in murine colon adenocarcinoma and melanoma cancer models

Forde, Patrick F, Hall, Lindsay, de Kruijf, Marcel, Bourke, M G, Doddy, T, Sadadcharam, Mira and Soden, Declan M (2015) Non-viral immune electro-gene therapy induces potent anti-tumour responses and has a curative effect in murine colon adenocarcinoma and melanoma cancer models. Gene Therapy, 22. 29–39. ISSN 0969-7128

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Abstract

Antitumour efficacy of electroporated pEEV, coding for granulocyte–macrophage colony-stimulating factor and the B7-1 costimulatory immune molecule (pEEVGmCSF-b7.1) in growing solid tumours, was investigated and compared with a standard plasmid. Application of pEEVGmCSF-b7.1 led to complete tumour regression in 66% of CT26-treated tumours and 100% in the B16F10-treated tumours at day 150 post-treatment. pEEVGmCSF-b7.1 treatment was found to significantly enhance levels of both innate and adaptive immune populations in tumour and systemic sites, which corresponded to significantly increased tissue levels of proinflammatory cytokines including interferon-γ (IFN-γ) and interleukin-12 (IL-12). In contrast, pEEVGmCSF-b7.1 treatment significantly reduced the T-regulatory populations and also the anti-inflammatory cytokine IL-10. Upon further characterisation of functional immune responses, we observed a significant increase in cytotoxic (CD107a+) and IFN-γ-producing natural killer cells and also significantly more in IL-12-producing B cells. Importantly, splenocytes isolated from pEEVGmCSF-b7.1-treated ‘cured’ mice were tumour-specific and afforded significant protection in a tumour rechallenge model (Winn assay). Our data indicate that electroimmunogene therapy with the non-viral pEEVGmCSF-b7.1 is able to induce potent and durable antitumour immune responses that significantly reduce primary and also secondary tumour growth, and thus represents a solid therapeutic platform for pursuing future clinical trials.

Item Type: Article
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Faculty \ School: University of East Anglia > Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 22 Apr 2015 13:38
Last Modified: 25 Jul 2018 10:05
URI: https://ueaeprints.uea.ac.uk/id/eprint/53249
DOI: 10.1038/gt.2014.95

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