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. The aim of successful lung cancer treatment is to totally eliminate the tumour and the risk of recurrence. Lung cancer treatment currently relies on removal of the tumour by surgery or radiotherapy, followed by chemotherapy to destroy of 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) with the aim of eliminating the tumour non-invasively and recruiting an immune response against any remaining cancer cells.

Published Papers

1.  Bendix, M. B., Brint, E., & Forde, P. F. (2021). Electroporation of suspension cell lines – A proposed assay set for optimizations. Bioelectrochemistry, 142, 107891. https://doi.org/10.1016/j.bioelechem.2021.107891

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 into different cancer cell types. It showed that each cancer cell type has an optimal electric field strengths that is cell line and not cancer type dependent.

2. 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. https://doi.org/10.1016/j.ejso.2022.05.023

Lay Summary: This is an overview of the published literature about the use of electrchometherapy 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 effectivness of electrochemotherapy more research needs to be carried out to understand the impacts on the immune system as well as immune cells.

3. 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. https://doi.org/10.1016/j.bioelechem.2022.108257

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.

4. Bendix, M. Baker KJ, B., Forde, P. F., Houston, A., & Brint, E. Functional and cellular responses of dendritic cells post electrochemortherapy treatment is dependant on electric field strength. Manuscript in Preparation

Lay Summary: Treatment of tumours with electrochemotherapy, the application of an electric field to deliver chemotherapy drugs inside cancer cells, has the potential to significantly affect the makeup of surrounding cells of the tumour, which includes immune cells. This is important, as immune cells are critical to the anti-cancer immune response. In this manuscript, we investigate the effect of electrochemotherapy on an important immune cell type termed dendritic cells and demonstrate that whilst electrochemotherapy treatment results in dendritic cell death, those cells that survive are functional and able to respond. Importantly the different electric field strengths applied to the cells resulted in different levels of cell death and different functional responses meaning that electrochemotherapy protocols for patients could be improved to increase levels of immune cell survival and help the anti-cancer immune response.

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.

Attended Conferences:

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

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.