Exploring a novel cell therapy for lung cancer
Lead Research Organisation:
University College London
Department Name: Medicine
Abstract
Lung cancer is the third most common type of cancer in the UK and the leading cause of cancer death worldwide (CRUK, 2018). As many patients present with advanced disease, current treatment options provide limited efficacy and the overall survival rate at 5 years is just 10%. Research into alternative treatments is ongoing and TNF-related apoptosis-inducing ligand (TRAIL) has attracted a lot of interest in this context.
TRAIL activates the extrinsic apoptosis pathway and displays selectivity towards tumour cells, leaving bystander healthy cells intact. The group has previously transduced mesenchymal stem cells (MSCs) to express TRAIL, creating a cell therapy product capable of homing to the site of the tumour and inducing apoptosis in the malignant cells upon binding of TRAIL to its receptor (Loebinger, et al., 2009). This therapy, MSC-TRAIL, will enter a phase I/II clinical trial, providing an opportunity to address unanswered questions related to the efficacy of the therapy. Notably, these will include investigating the biodistribution and persistence of cells after administration, profiling of any immune response induced and identification of biomarkers for MSC homing.
Furthermore, this project will explore the interactions of MSCs, and specifically MSC-TRAIL, within the tumour microenvironment. Although some studies have shown pro-tumorigenic properties of MSCs, notably by promoting stemness of cancerous cells, many other studies have shown the cells to inhibit tumour growth (Rhee, et al., 2015). These studies suggest that MSCs suppress tumour growth through several mechanisms, including promoting immune cell infiltration and inducing cell cycle arrest in malignant cells. Untangling these associations is of importance to MSC-TRAIL and, more broadly, for employing MSCs for cancer therapy.
Overall, this project aims to further explore the use of MSC-TRAIL as a therapeutic for lung cancer. This will be done both through defining unknown aspects of MSC-TRAIL therapy in patients, as well as characterising the interactions of MSCs in the tumour microenvironment.
References
CRUK, 2018. Lung Cancer Stastics. [Online]
Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer
Kolluri, K. et al., 2018. Loss of functional BAP1 augments sensitivity to TRAIL in cancer cells.. Elife.
Loebinger, M., Eddaoudi, A., Davies, D. & Janes, S., 2009. Mesenchymal stem cell delivery of TRAIL can eliminate metastatic cancer. Cancer Research.
Rhee, K., Lee, J. & Eom, Y., 2015. Mesenchymal stem cell-mediated effects of tumour support or suppression. International Journal of Molecular Sciences.
TRAIL activates the extrinsic apoptosis pathway and displays selectivity towards tumour cells, leaving bystander healthy cells intact. The group has previously transduced mesenchymal stem cells (MSCs) to express TRAIL, creating a cell therapy product capable of homing to the site of the tumour and inducing apoptosis in the malignant cells upon binding of TRAIL to its receptor (Loebinger, et al., 2009). This therapy, MSC-TRAIL, will enter a phase I/II clinical trial, providing an opportunity to address unanswered questions related to the efficacy of the therapy. Notably, these will include investigating the biodistribution and persistence of cells after administration, profiling of any immune response induced and identification of biomarkers for MSC homing.
Furthermore, this project will explore the interactions of MSCs, and specifically MSC-TRAIL, within the tumour microenvironment. Although some studies have shown pro-tumorigenic properties of MSCs, notably by promoting stemness of cancerous cells, many other studies have shown the cells to inhibit tumour growth (Rhee, et al., 2015). These studies suggest that MSCs suppress tumour growth through several mechanisms, including promoting immune cell infiltration and inducing cell cycle arrest in malignant cells. Untangling these associations is of importance to MSC-TRAIL and, more broadly, for employing MSCs for cancer therapy.
Overall, this project aims to further explore the use of MSC-TRAIL as a therapeutic for lung cancer. This will be done both through defining unknown aspects of MSC-TRAIL therapy in patients, as well as characterising the interactions of MSCs in the tumour microenvironment.
References
CRUK, 2018. Lung Cancer Stastics. [Online]
Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer
Kolluri, K. et al., 2018. Loss of functional BAP1 augments sensitivity to TRAIL in cancer cells.. Elife.
Loebinger, M., Eddaoudi, A., Davies, D. & Janes, S., 2009. Mesenchymal stem cell delivery of TRAIL can eliminate metastatic cancer. Cancer Research.
Rhee, K., Lee, J. & Eom, Y., 2015. Mesenchymal stem cell-mediated effects of tumour support or suppression. International Journal of Molecular Sciences.
