UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Therapeutic breast reconstruction using gene therapy delivered IFN-gamma immunotherapy

Davis, CR; Than, PA; Khong, SML; Rodrigues, M; Findlay, MW; Navarrete, DJ; Ghali, S; ... Gurtner, GC; + view all (2019) Therapeutic breast reconstruction using gene therapy delivered IFN-gamma immunotherapy. Molecular Cancer Therapeutics 10.1158/1535-7163.mct-19-0315. (In press).

[img] Text
Vaidya_10.1158 --1535-7163.MCT-19-0315.pdf - Accepted version
Access restricted to UCL open access staff until 29 October 2020.

Download (1MB)

Abstract

After mastectomy, breast reconstruction is increasingly performed using autologous tissue with the aim of improving quality of life. During this procedure, autologous tissue is excised, relocated, and reattached using vascular anastomoses at the site of the extirpated breast. The period during which the tissue is ex vivo may allow genetic modification without any systemic exposure to the vector. Could such access be used to deliver therapeutic agents using the tissue flap as a vehicle? Such delivery may be more efficient than systemic treatment, in terms of oncological outcomes. The cytokine interferon gamma (IFNγ) has antitumor effects, but systemic toxicity that could be circumvented if its effect can be localized by delivery of the IFNγ gene via gene therapy to autologous tissue used for breast reconstruction, which then releases IFNγ and exerts anti-tumor effects. In a rat model of loco-regional recurrence (LRR) using both MADB-106-Luc and MAD-MB-231-Luc breast cancer cells, autologous tissue was transduced ex vivo with an adeno-associated viral vector (AAV) encoding IFNγ. The therapeutic reconstruction released IFNγ at the LRR site and eliminated cancer cells, significantly decreased tumor burden (P<0.05), and increased survival by 33% (P<0.05) compared to sham reconstruction. Mechanistically, localized IFNγ immunotherapy stimulated M1 macrophages to target cancer cells within the regional confines of the modified tumor environment. This concept of therapeutic breast reconstruction using ex vivo gene therapy of autologous tissue offers a new application for immunotherapy in breast cancer with a dual therapeutic effect of both reconstructing the ablative defect and delivering local adjuvant immunotherapy.

Type: Article
Title: Therapeutic breast reconstruction using gene therapy delivered IFN-gamma immunotherapy
DOI: 10.1158/1535-7163.mct-19-0315
Publisher version: https://doi.org/10.1158/1535-7163.mct-19-0315
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention
URI: https://discovery.ucl.ac.uk/id/eprint/10084569
Downloads since deposit
1Download
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item