Gene Immunotherapy of Colon Carcinoma with IL-2 and IL-12 Using Gene Electrotransfer.
Tilen KomelMasa OmerzelUrška KamenšekKatarina ZnidarUrsa Lampreht TratarSimona Kranjc BrezarKlemen DolinarSergej PirkmajerGregor SersaMaja CemazarPublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- combination therapy
- genome wide
- genome wide identification
- copy number
- computed tomography
- escherichia coli
- image quality
- randomized controlled trial
- blood pressure
- magnetic resonance imaging
- dna methylation
- high fat diet induced
- genome wide analysis
- squamous cell carcinoma
- transcription factor
- metabolic syndrome
- contrast enhanced
- positron emission tomography
- skeletal muscle
- squamous cell
- multidrug resistant
- insulin resistance
- newly diagnosed
- wild type