Povzetek
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.
Ključne besede
genska terapija;genski elektroprenos;IL-12;imunoterapija;melanom;gene therapy;gene electrotransfer;immunotherapy;melanoma;
Podatki
Jezik: |
Angleški jezik |
Leto izida: |
2021 |
Tipologija: |
1.01 - Izvirni znanstveni članek |
Organizacija: |
OI - Onkološki inštitut Ljubljana |
Založnik: |
Elsevier |
UDK: |
602.6/.7 |
COBISS: |
67179011
|
ISSN: |
1567-5394 |
Št. ogledov: |
39 |
Št. prenosov: |
23 |
Ocena: |
0 (0 glasov) |
Metapodatki: |
|
Ostali podatki
Sekundarni jezik: |
Slovenski jezik |
Sekundarne ključne besede: |
genska terapija;genski elektroprenos;IL-12;imunoterapija;melanom; |
Strani: |
str. 107843-1-107843-16 |
Zvezek: |
ǂVol. ǂ141 |
Čas izdaje: |
Oct. 2021 |
DOI: |
10.1016/j.bioelechem.2021.107843 |
ID: |
16542985 |