Gene Immunotherapy of Colon Carcinoma with IL-2 and IL-12 Using Gene Electrotransfer

Author:

Komel Tilen12,Omerzel Masa1,Kamensek Urska1ORCID,Znidar Katarina1,Lampreht Tratar Ursa1ORCID,Kranjc Brezar Simona1ORCID,Dolinar Klemen3ORCID,Pirkmajer Sergej3ORCID,Sersa Gregor14ORCID,Cemazar Maja15ORCID

Affiliation:

1. Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana, Slovenia

2. Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana, Slovenia

3. Faculty of Medicine, Institute of Pathophysiology, University of Ljubljana, Zaloska 4, SI-1000 Ljubljana, Slovenia

4. Faculty of Health Sciences, University of Ljubljana, Zdravstvena pot 5, SI-1000 Ljubljana, Slovenia

5. Faculty of Health Sciences, University of Primorska, Polje 42, SI-6310 Izola, Slovenia

Abstract

Gene immunotherapy has become an important approach in the treatment of cancer. One example is the introduction of genes encoding immunostimulatory cytokines, such as interleukin 2 and interleukin 12, which stimulate immune cells in tumours. The aim of our study was to determine the effects of gene electrotransfer of plasmids encoding interleukin 2 and interleukin 12 individually and in combination in the CT26 murine colon carcinoma cell line in mice. In the in vitro experiment, the pulse protocol that resulted in the highest expression of IL-2 and IL-12 mRNA and proteins was used for the in vivo part. In vivo, tumour growth delay and also complete response were observed in the group treated with the plasmid combination. Compared to the control group, the highest levels of various immunostimulatory cytokines and increased immune infiltration were observed in the combination group. Long-term anti-tumour immunity was observed in the combination group after tumour re-challenge. In conclusion, our combination therapy efficiently eradicated CT26 colon carcinoma in mice and also generated strong anti-tumour immune memory.

Funder

Slovenian Research and Innovation Agency

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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