135P - Coxsackievirus type B3 is a potent oncolytic virus against KRAS-mutant non-small cell lung cancer

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Non-Small-Cell Lung Cancer, Metastatic
Lung and other Thoracic Tumours
Presenter Haoyu Deng
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors H. Deng1, T.D. Sliva2, Y. Xue3, Y. Mohamud3, J. Zhang3, W. Lockwood2, H. Luo3
  • 1Department Of Pathology And Laboratory Medicine, Center for Heart and Lung Innovation, St.Paul's Hospital, V6Z 1Y6 - Vancouver/CA
  • 2British Columbia Cancer Agency, Vancouver/CA
  • 3Department Of Pathology And Laboratory Medicine, Center for Heart and Lung Innovation, St.Paul's Hospital, Vancouver/CA

Abstract

Background

Lung cancer is one of the most leading causes of cancer-related death worldwide. Over 85% of lung cancers are non-small cell lung cancer (NSCLC), for which the 5-year survival rate is extremely low (∼15.9%). Most NSCLCs are caused by the accumulation of genomic alterations, among which epidermal growth factor receptor (EGFR) mutation and KRAS mutation are two of the most predominant types. Although patients with EGFR-mutant NSCLCs have manifested a good response to EGFR inhibitors, there is a paucity of effective treatments for the KRAS-mutant NSCLCs and new strategies are urgently needed. Coxsackievirus type B3 (CV-B3) is a non-enveloped, human-pathogenic enterovirus that causes mild flu-like symptoms in adults. Due to its highly lytic nature, CV-B3 has yielded an increased efficacy of viral-mediated oncolysis as compared to other viruses, which makes it as a good candidate for cancer treatment.

Methods

Seven NSCLC cell lines (A549, H2030, H23, H1975, PC-9, H3255 and HCC4006) and three normal lung epithelial cells (HPL1D, HAE and BEAS2B) were selected for this study. Cells were infected with CV-B3 (MOI 0.01) for 48hrs. Cytopathic effects caused by virus infection were observed by light microscope, followed by crystal violet staining. MTS assay were conducted to examine the resistance of normal lung epithelial cells upon CVB3 infection. The supernatants were collected to determine the virus titres by plaque assay. Coxsackievirus and adenovirus receptor (CAR) expression was examined via western blot.

Results

Our studies found that CV-B3 treatment led to a significant reduction of cell survival in KRAS-mutant NSCLCs but not EGFR-mutant NSCLCs nor normal lung epithelial cells. MTS assay results demonstrated CV-B3 infection didn’t lead to a significant enhancement of cell death in normal lung epithelial cells. Furthermore, we showed that virus titres within the supernatants of KRAS-mutant NSCLCs are significantly higher than both EGFR-mutant NSCLCs and normal lung epithelial cells. Finally, we demonstrated that CAR expression levels were significantly increased in KRAS-mutant NSCLCs.

Conclusions

Our study found that CV-B3 is an effective and safe oncolytic virus against KRAS-mutant NSCLCs.

Clinical trial identification

Legal entity responsible for the study

Center for Heart and Lung Innovation, St. Paul’s Hospital, Department of Pathology and Laboratory Medicine, University of British Columbia

Funding

British Columbia Lung Association

Disclosure

All authors have declared no conflicts of interest.