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Title:Mutational burden, MHC-I expression and immune infiltration as limiting factors for in situ vaccination by TNF[alfa] and IL-12 gene electrotransfer
Authors:ID Kamenšek, Urška (Author)
ID Uršič Valentinuzzi, Katja (Author)
ID Markelc, Boštjan (Author)
ID Čemažar, Maja (Author)
ID Šetrajčič Dragoš, Vita (Author)
ID Serša, Gregor (Author)
Files:.pdf PDF - Presentation file, download (1,78 MB)
MD5: DDCAFACD2C692465513B2DD33C2266FD
 
Language:English
Typology:1.01 - Original Scientific Article
Organization:Logo OI - Institute of Oncology
Abstract:In situ vaccination is a promising immunotherapeutic approach, where various local ablative therapies are used to induce an immune response against tumor antigens that are released from the therapy-killed tumor cells. We recently proposed using intratumoral gene electrotransfer for concomitant transfection of a cytotoxic cytokine tumor necrosis factor-% (TNF%) to induce in situ vaccination, and an immunostimulatory cytokine interleukin 12 (IL-12) to boost the primed immune response. Here, our aim was to test the local and systemic effectiveness of the approach in tree syngeneic mouse tumor models and associate it with tumor immune profiles, characterized by tumor mutational burden, immune infiltration and expression of PD-L1 and MHC-I on tumor cells. While none of the tested characteristic proved predictive for local effectiveness, high tumor mutational burden, immune infiltration and MHC-I expression were associated with higher abscopal effectiveness. Hence, we have confirmed that both the abundance and presentation of tumor antigens as well as the absence of immunosuppressive mechanisms are important for effective in situ vaccination. These findings provide important indications for future development of in situ vaccination based treatments, and for the selection of tumor types that will most likely benefit from it.
Keywords:in situ vaccination, gene electrotransfer, interleukin 12, tumor necrosis factor [alfa]
Publication status:Published
Publication version:Version of Record
Publication date:28.04.2021
Publisher:Elsevier
Year of publishing:2021
Number of pages:str. 1-107831-10-107831
Numbering:Vol. 140
PID:20.500.12556/DiRROS-15561 New window
UDC:602.6/.7
ISSN on article:1567-5394
DOI:10.1016/j.bioelechem.2021.107831 New window
COBISS.SI-ID:61967107 New window
Copyright:by Authors
Publication date in DiRROS:19.09.2022
Views:506
Downloads:164
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Record is a part of a journal

Title:Bioelectrochemistry
Publisher:Elsevier
ISSN:1567-5394
COBISS.SI-ID:2502484 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:P3-0003-2015
Name:Razvoj in ovrednotenje novih terapij za zdravljenje malignih tumorjev

Funder:ARRS - Slovenian Research Agency
Project number:J3-2528-2020
Name:Imunski genski elektroprenos IL-12 in IL-2 za zdravljenje immunološko hladnih/vročih tumorjih

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:17.09.2022

Secondary language

Language:Slovenian
Keywords:cepljenje in situ, genski elektrotransfer, interlevkin 12, dejavnik tumorske nekroze [alfa]


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