Enhancement of electroporation facilitated immunogene therapy via T-reg depletion

Forde, Patrick F, Sadadcharam, Mira, Hall, Lindsay J, O'Donovan, T R, de Kruijf, Marcel, Byrne, William L, O'Sullivan, Gerald C and Soden, Declan M (2014) Enhancement of electroporation facilitated immunogene therapy via T-reg depletion. Cancer Gene Therapy, 21. pp. 349-354. ISSN 0929-1903

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    Abstract

    Regulatory T cells (T-regs) can negatively impact tumor antigen-specific immune responses after infiltration into tumor tissue. However, depletion of T-regs can facilitate enhanced anti-tumor responses, thus augmenting the potential for immunotherapies. Here we focus on treating a highly aggressive form of cancer using a murine melanoma model with a poor prognosis. We utilize a combination of T-reg depletion and immunotherapy plasmid DNA delivered into the B16F10 melanoma tumor model via electroporation. Plasmids encoding murine granulocyte macrophage colony-stimulating factor and human B71 were transfected with electroporation into the tumor and transient elimination of T-regs was achieved with CD25-depleting antibodies (PC61). The combinational treatment effectively depleted T-regs compared to the untreated tumor and significantly reduced lung metastases. The combination treatment was not effective in increasing the survival, but only effective in suppression of metastases. These results indicate the potential for combining T-reg depletion with immunotherapy-based gene electrotransfer to decrease systemic metastasis and potentially enhance survival.

    Item Type: Article
    Additional Information: This work is licensed under a Creative Commons Attribution 3.0 Unported License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/
    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
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    Depositing User: Pure Connector
    Date Deposited: 20 Aug 2014 09:42
    Last Modified: 25 Jul 2018 09:59
    URI: https://ueaeprints.uea.ac.uk/id/eprint/49956
    DOI: 10.1038/cgt.2014.35

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