Tilen Komel (Avtor), Maša Bošnjak (Avtor), Simona Kranjc (Avtor), Mariangela De Robertis (Avtor), M. Mastrodonato (Avtor), G. Scillitani (Avtor), G. Pesole (Avtor), Emanuella Signori (Avtor), Gregor Serša (Avtor), Maja Čemažar (Avtor)

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:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: OI - Onkološki inštitut Ljubljana
Založnik: Elsevier
UDK: 602.6/.7
COBISS: 67179011 Povezava se bo odprla v novem oknu
ISSN: 1567-5394
Št. ogledov: 39
Št. prenosov: 23
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

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