Gene electrotransfer of IL-2 and IL-12 plasmids effectively eradicated murine B16.F10 melanoma

被引:0
作者
Komel T. [1 ,2 ]
Bosnjak M. [1 ]
Kranjc Brezar S. [1 ,2 ]
De Robertis M. [3 ]
Mastrodonato M. [4 ]
Scillitani G. [4 ]
Pesole G. [3 ,5 ]
Signori E. [6 ]
Sersa G. [1 ,7 ]
Cemazar M. [1 ,8 ]
机构
[1] Institute of Oncology Ljubljana, Department of Experimental Oncology, Zaloska 2, Ljubljana
[2] University of Ljubljana, Faculty of Medicine, Vrazov trg 2, Ljubljana
[3] Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, Via Orabona 4, Bari
[4] Department of Biology, University of Bari, Via Orabona 4, Bari
[5] National Research Council-Institute of Biomembrane, Bioenergetics, and Molecular Biotechnology (CNR-IBIOM), Via Amendola 122 O, Bari
[6] National Research Council-Institute of Translational Pharmacology (CNR-IFT), Via Fosso del Cavaliere 100, Rome
[7] University of Ljubljana, Faculty of Health Sciences, Zdravstvena pot 5, Ljubljana
[8] University of Primorska, Faculty of Health Sciences, Polje 42, Izola
来源
Cemazar, M. (mcemazar@onko-i.si) | 1600年 / Elsevier B.V.卷 / 141期
关键词
Gene electrotransfer; Gene therapy; IL-12; IL-2; Immunotherapy; Melanoma;
D O I
10.1016/j.bioelechem.2021.107843
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学科分类号
摘要
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 µs, 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. © 2021 The Author(s)
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