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Gene electrotransfer of IL-2 and IL-12 plasmids effectively eradicated murine B16.F10 melanomaKomel, Tilen ...Gene therapy has become an important approach for treating cancer, and electroporation represents a technology for introducing therapeutic genes into a cell. An example of cancer gene therapy relying ... on gene electrotransfer is the use of immunomodulatory cytokines, such as interleukin 2 (IL-2) and 12 (IL-12), which directly stimulate immune cells at the tumour site. The aim of our study was to determine the effects of gene electrotransfer with two plasmids encoding IL-2 and IL-12 in vitro and in vivo. Two different pulse protocols, known as EP1 (600 V/cm, 5 ms, 1 Hz, 8 pulses) and EP2 (1300 V/cm, 100 %s, 1 Hz, 8 pulses), were assessed in vitro for application in subsequent in vivo experiments. In the in vivo experiment, gene electrotransfer of pIL-2 and pIL-12 using the EP1 protocol was performed in B16.F10 murine melanoma. Combined treatment of tumours using pIL2 and pIL12 induced significant tumour growth delay and 71% complete tumour regression. Furthermore, in tumours coexpressing IL-2 and IL-12, increased accumulation of dendritic cells and M1 macrophages was obtained along with the activation of proinflammatory signals, resulting in CD4 + and CD8 + T-lymphocyte recruitment and immune memory development in the mice. In conclusion, we demonstrated high antitumour efficacy of combined IL-2 and IL-12 gene electrotransfer protocols in low-immunogenicity murine B16.F10 melanoma.Source: Bioelectrochemistry. - ISSN 1567-5394 (Vol. 141, Oct. 2021, str. 107843-1-107843-16)Type of material - article, component partPublish date - 2021Language - englishCOBISS.SI-ID - 67179011
Author
Komel, Tilen |
Omerzel, Maša, mag. farm. |
Kranjc Brezar, Simona |
De Robertis, Mariangela |
Mastrodonato, M. |
Scillitani, G. |
Pesole, G. |
Signori, Emanuella |
Serša, Gregor |
Čemažar, Maja
Topics
genska terapija |
genski elektroprenos |
IL-12 |
imunoterapija |
melanom |
gene therapy |
gene electrotransfer |
IL-12 |
immunotherapy |
melanoma
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Author | Komel, Tilen ... |
Title | Gene electrotransfer of IL-2 and IL-12 plasmids effectively eradicated murine B16.F10 melanoma |
Publication date | 2021-05-18 |
COBISS.SI-ID | 67179011 |
Publication version in repository | Publisher's version |
Publication licence | Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International |
Embargo | Immediate publication for public |
Project(s) from which the publication was funded
Title | Acronym | Project ID | Funder |
---|---|---|---|
Spremljanje imunskega odziva v realnem času po in situ vakcinaciji z elektrokemoterapijo in pridruženo gensko terapijo z interlevkinom-12 | J3-8202-2017 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Razvoj in ovrednotenje novih terapij za zdravljenje malignih tumorjev | P3-0003-2015 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Imunski genski elektroprenos IL-12 in IL-2 za zdravljenje immunološko hladnih/vročih tumorjih | J3-2528-2020 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
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Komel, Tilen | 53504 |
Omerzel, Maša, mag. farm. | 34373 |
Kranjc Brezar, Simona | 19058 |
De Robertis, Mariangela | ![]() |
Mastrodonato, M. | ![]() |
Scillitani, G. | ![]() |
Pesole, G. | ![]() |
Signori, Emanuella | ![]() |
Serša, Gregor | 08800 |
Čemažar, Maja | 14575 |
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