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Published on: January 19, 2018
Visualization of Nonspecific Antitumor Effectiveness and Vascular Effects of Gene Electro-Transfer to Tumors
Urska Kamensek, Marie-Pierre Rols, Maja Cemazar1
1Department of Experimental Oncology, Institute of Oncology Ljubljana, SI- 1000 Ljubljana, Slovenia. mcemazar@onko-i.si.
Background:
Gene Electro Transfer (GET) is a promising method for therapeutic purposes. Intratumoral GET has reached clinical evaluation for antitumor treatment. An increasing number of studies suggests that antitumor effectiveness not only depends on the transfection efficiency, but also on the induction of immune responses and vascular effects that result in the nonspecific induction of cell death. Real time noninvasive optical imaging methods allow longitudinal studies of these dynamic biological processes.
Objective:
In the present study, a noninvasive bioluminescence technology was used to further explore the phenomena associated with GET to tumors by a real time monitoring of the transfection efficiency as well as cell death following the treatment.
Method:
By using transgenic light-producing tumors, tumor growth was visualized, and since dead cells stop producing light, effectiveness of the treatment or the emergence of necrotic areas in the tumors was followed visually. The transfection efficiency of reporter genes (iRFP protein and luciferase) in the subcutaneous tumors was also evaluated.
Results:
Our results showed that the GET of a reporter gene can lead to nonspecific antitumor effectiveness and even complete regression of tumors. Using light-producing tumors, we were also able to indirectly visualize the previously described vascular effects of electroporation. Additionally, using the intratumoral GET of a luciferase encoding plasmid, we localized the source of the expression mainly in the peritumoral and not in the tumoral region.
Conclusion:
The data obtained provide new insights into some of the phenomena associated with GET to tumors, which should be taken into account when designing improved and more effective cancer gene therapy, in order to accelerate the transfer of the technology into clinical trials.
Insights
Gene Electro Transfer (GET) shows promise for cancer therapy, leading to tumor regression through gene delivery and immune responses. Noninvasive imaging tracked transfection efficiency and cell death, aiding future cancer gene therapy development.
Area of Science:
- Biotechnology
- Oncology
- Medical Imaging
Background:
- Gene Electro Transfer (GET) is a promising therapeutic method with clinical evaluation for antitumor treatment.
- Antitumor effectiveness of GET depends on transfection efficiency, immune responses, and vascular effects causing cell death.
- Noninvasive optical imaging enables longitudinal studies of dynamic biological processes in tumors.
Purpose of the Study:
- To explore phenomena associated with GET to tumors using noninvasive bioluminescence technology.
- To monitor transfection efficiency and cell death in real-time following GET treatment.
- To investigate the potential for nonspecific antitumor effects and vascular changes induced by GET.
Main Methods:
- Utilized transgenic light-producing tumors for real-time visualization of tumor growth and cell death.
- Assessed transfection efficiency of reporter genes (iRFP, luciferase) in subcutaneous tumors.
- Employed bioluminescence imaging to monitor treatment effectiveness and visualize vascular effects.
Main Results:
- GET of reporter genes demonstrated nonspecific antitumor effectiveness, leading to complete tumor regression in some cases.
- Bioluminescence imaging visualized vascular effects of electroporation, previously described.
- Intratumoral GET of luciferase plasmid showed primary expression in the peritumoral region, not within the tumor.
Conclusions:
- GET can induce nonspecific antitumor effects and tumor regression, highlighting its therapeutic potential.
- Real-time imaging provides insights into GET-induced vascular effects and gene expression patterns.
- Findings offer valuable information for designing more effective cancer gene therapies and accelerating clinical translation.
