Combining electrochemotherapy with a Toll Like receptor agonist for the treatment of lung cancer

Lung cancer is the leading cause of cancer death among men and women in Ireland. Successful lung cancer treatment aims to totally eliminate the tumour and the risk of recurrence. Lung cancer treatment currently relies on the removal of the tumour by surgery or radiotherapy, followed by chemotherapy to destroy any remaining cancer cells which may be circulating in the body. At CancerResearch@UCC we have been examining these two aspects of treatment (removal of the tumour and the cancer cells circulating in the body) to eliminate the tumour non-invasively and recruit an immune response against any remaining cancer cells.

Research Findings

Publications

Bendix, M. B., Houston, A., Forde, P. F., & Brint, E. (2022b). Electrochemotherapy and immune interactions; A boost to the system? European Journal of Surgical Oncology.

Lay Summary: This is an overview of the published literature about the use of electrochemotherapy as anti-cancer therapy. The procedure has been investigated since the early 1990s and is since 2006 a standard of care option for melanoma patients while it is still under clinical trial for further cancer types. To further improve the effectiveness of electrochemotherapy more research needs to be carried out to understand the impacts on the immune system as well as immune cells.

Bendix, M. B., Houston, A., Forde, P. F., & Brint, E. (2022). Defining optimal parameters to maximize the effect of electrochemotherapy on lung cancer cells whilst preserving the integrity of immune cells. Bioelectrochemistry, 148, 108257.

Lay Summary: Electrochemotherapy, the application of an electric field to deliver chemotherapy drugs inside cancer cells, was investigated as a potential treatment for lung cancer patient by determining the impact electrochemotherapy has on lung cancer cell lines and immune cells in the laboratory. The research showed that lung cancer cell lines could be sufficiently negatively affected by electrochemotherapy with cisplatin, a commonly used chemo drug for lung cancer treatment. Furthermore our research showed that not only lung cancer cells can get negatively impacted but also different types of immune cells. Thus, further research is needed to find the right balance between cancer cell killing and protecting the immune cells to get optimal treatment results.

Bendix, M. B., Brint, E., & Forde, P. F. (2021). Electroporation of suspension cell lines – A proposed assay set for optimizations. Bioelectrochemistry, 142, 107891.

Lay Summary: Electroporation, the application of an electric field, is used to deliver drugs and genes into a cell, for example, electroporation can be used to deliver chemo drugs targeted into cancer cells. In this paper, we presented a set of analysis methods to determine the best electric field strengths to use to deliver drugs to different cancer cell types. It showed that each cancer cell type has an optimal electric field strength that is cell-line and not cancer-type dependent.

Tremble LF, O’Brien MA, Soden DM, Forde PF. Electrochemotherapy with cisplatin increases survival and induces immunogenic responses in murine models of lung cancer and colorectal cancer. Cancer Lett. 2019 Feb 1;442:475-482. doi: 10.1016/j.canlet.2018.11.015. Epub 2018 Nov 22. PMID: 30472183.

Presentations

Oral Presentation 

3^rd World Congress on electroporation-based therapies and treatments, 2-6 September 2019, Toulouse, France, Effect of EP and ECT on immune cells- In vitro study

4^th World Congress on electroporation-based therapies and treatments, 9-13 October 2022, Copenhagen, Denmark, Impact of electrochemotherapy on immune cells in the context of cancer – In vitro study

Poster Presentation

Breaking Through: research to Transform Cancer Treatment, 5- 6 September 2019, Cork, Ireland, Optimizing of ECT parameters for human lung cancer cell lines and their influence on TLR expression patterns

Irish Society for Immunology Annual Meeting 2019, 19 and 20 September 2019, Dublin, Ireland, Optimizing of ECT parameters for human lung cancer cell lines and their influence on TLR expression patterns

The 58^th Annual IACR conference, March 30 – April 1, 2022, Cork, Ireland, Differential responses of immune cells and lung cancer cells to electroporation and electrochemotherapy in vitro

The image below shows Maura (7th from the right) at the World Congress on electroporation-based therapies and treatments in Toulouse, where she presented her research in 2019.