TFRI researchers have identified that a virus commonly associated with hand, foot and mouth disease in children can significantly reduce the size of lung adenocarcinomas displaying a specific mutation in mice.
The findings about Coxsackievirus Type B3 (CVB3) could lead to the development of new treatments for the nearly 25 per cent of lung cancer patients that exhibit KRAS mutations (KRASmut) who currently have no treatment options.
“In this study we showed that wild-type (WT) CVB3 specifically targets KRASmut lung adenocarcinoma cells with limited effects on normal lung epithelial cells,” writes co-senior author and former Terry Fox New Investigator Dr. William Lockwood, a scientist at BC Cancer. The work was published in Molecular Therapy: Oncolytics (September 2019).
The use of viruses to fight cancer is not new. Some viruses, like the herpes simplex virus, have already been approved for use in cancer therapy. These viruses, which are known as oncolytic viruses (OVs), are often able to exploit certain vulnerabilities that are unique to cancer cells, allowing them to quickly grow within those cells.
The team hypothesized that CVB3 could do something similar by hijacking a specific signaling pathway in KRASmut lung adenocarcinoma cells known as ERK1/2. By exploiting this pathway, the team believed that the virus could replicate within the cancer cell (but not in other cells), eventually killing them off.
The team tested this theory by using immunocompromised mice models and found that intratumoural injection of CVB3 effectively managed to kill off the KRASmut lung adenocarcinoma cells, sparing healthy cells in the area. This resulted in a significant reduction in KRASmut tumour size in the mice.
“We demonstrated why this specific mutation makes cancer cells sensitive to CVB3-induced cytotoxicity - they have increased ERK1/2 activation and impaired type I interferon response,” said Dr. Lockwood. “These findings suggest that CVB3 may provide an excellent candidate for the development of targeted therapies for lung cancer and are pushing us to engineer CVB3 to further increase its selectivity for lung cancer cells and decrease any potential normal cell toxicities that remain.”
Coxsackievirus Type B3 Is a Potent Oncolytic Virus against KRAS-Mutant Lung Adenocarcinoma
Haoyu Deng, Huitao Liu, Tanya de Silva, YuanChao Xue, Yasir Mohamud, Chen Seng Ng, Junyan Qu, Jingchun Zhang, William W.G. Jia, William W. Lockwood, and Honglin Luo
This study is partially funded by a Terry Fox New Investigator Award to Dr. William Lockwood.