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Title:Potentiation of electrochemotherapy effectiveness by immunostimulation with IL-12 gene electrotransfer in mice is dependent on tumor immune status
Authors:ID Uršič Valentinuzzi, Katja (Author)
ID Kos, Špela (Author)
ID Kamenšek, Urška (Author)
ID Čemažar, Maja (Author)
ID Miceska, Simona (Author)
ID Markelc, Boštjan (Author)
ID Buček, Simon (Author)
ID Starešinič, Barbara (Author)
ID Kloboves-Prevodnik, Veronika (Author)
ID Heller, Richard (Author)
ID Serša, Gregor (Author)
Files:.pdf PDF - Presentation file, download (7,82 MB)
MD5: 53FD7CD78C93640F8B5DBCA4938228C4
 
Language:English
Typology:1.01 - Original Scientific Article
Organization:Logo OI - Institute of Oncology
Abstract:Electrochemotherapy (ECT) exhibits high therapeutic effectiveness in the clinic, achieving up to 80% local tumor control but without a systemic (abscopal) effect. Therefore, we designed a combination therapy consisting of ECT via intratumoral application of bleomycin, oxaliplatin or cisplatin with peritumoral gene electrotransfer of a plasmid encoding interleukin-12 (p. t. IL-12 GET). Our hypothesis was that p. t. IL-12 GET potentiates the effect of ECT on local and systemic levels and that the potentiation varies depending on tumor immune status. Therefore, the combination therapy was tested in three immunologically different murine tumor models. In poorly immunogenic B16F10 melanoma, IL-12 potentiated the antitumor effect of ECT with biologically equivalent low doses of cisplatin, oxaliplatin or bleomycin. The most pronounced potentiation was observed after ECT using cisplatin, resulting in a complete response rate of 38% and an abscopal effect. Compared to B16F10 melanoma, better responsiveness to ECT was observed in more immunogenic 4%T1 mammary carcinoma and CT26 colorectal carcinoma. In both models, p. t. IL-12 GET did not significantly improve the therapeutic outcome of ECT using any of the chemotherapeutic drugs. Collectively, the effectiveness of the combination therapy depends on tumor immune status. ECT was more effective in more immunogenic tumors, but GET exhibited greater contribution in less immunogenic tumors. Thus, the selection of the therapy, namely, either ECT alone or combination therapy with p. t. IL-12, should be predominantly based on tumor immune status.
Keywords:electrochemotherapy, gene electrotransfer, interleukin-12
Publication status:Published
Publication version:Version of Record
Publication date:08.03.2021
Publisher:Elsevier
Year of publishing:2021
Number of pages:str. 623-635
Numbering:Vol. 332, no. 21
PID:20.500.12556/DiRROS-15569 New window
UDC:602.6/.7
ISSN on article:0168-3659
DOI:10.1016/j.jconrel.2021.03.009 New window
COBISS.SI-ID:54492931 New window
Copyright:by Authors
Publication date in DiRROS:21.09.2022
Views:1309
Downloads:437
Metadata:XML DC-XML DC-RDF
:
URŠIČ VALENTINUZZI, Katja, KOS, Špela, KAMENŠEK, Urška, ČEMAŽAR, Maja, MICESKA, Simona, MARKELC, Boštjan, BUČEK, Simon, STAREŠINIČ, Barbara, KLOBOVES-PREVODNIK, Veronika, HELLER, Richard and SERŠA, Gregor, 2021, Potentiation of electrochemotherapy effectiveness by immunostimulation with IL-12 gene electrotransfer in mice is dependent on tumor immune status. Journal of controlled release [online]. 2021. Vol. 332, no. 21, p. 623–635. [Accessed 10 April 2025]. DOI 10.1016/j.jconrel.2021.03.009. Retrieved from: https://dirros.openscience.si/IzpisGradiva.php?lang=eng&id=15569
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Record is a part of a journal

Title:Journal of controlled release
Shortened title:J. control. release
Publisher:Elsevier
ISSN:0168-3659
COBISS.SI-ID:27318784 New window

Document is financed by a project

Funder:ARRS - Slovenian Research Agency
Project number:J3-8202-2017
Name:Spremljanje imunskega odziva v realnem času po in situ vakcinaciji z elektrokemoterapijo in pridruženo gensko terapijo z interlevkinom-12
Funder:ARRS - Slovenian Research Agency
Project number:P3-0289-2019
Name:Značilnosti malignih neoplazem, pomembne za diagnozo ter napoved poteka bolezni in izida zdravljenja
Funder:ARRS - Slovenian Research Agency
Project number:P3-0003-2015
Name:Razvoj in ovrednotenje novih terapij za zdravljenje malignih tumorjev
Funder:ARRS - Slovenian Research Agency
Project number:Z3-2651-2020
Name:Elektrokemoterapija kot in situ vakcinacija

Licences

License:CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Link:http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Licensing start date:21.09.2022

Secondary language

Language:Slovenian
Keywords:elektrokemoterapija, elektroprenos genov, interlevkin-12


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