A Novel Oncolytic Viral Therapy Using Coxsackievirus B3 (CVB3) for Human Pancreatic Cancer Including Cancer-associated Fibroblasts.

Abstract

Background/aim: Pancreatic cancer is a major cause of mortality in the world. It is one of most aggressive diseases, with a 5-year survival rate of <10%. Cancer associated fibroblasts (CAFs) are the predominant non-cancer cells in pancreatic cancer tissues, playing a critical role in modulating the extracellular matrix (ECM). The ECM, maintained by CAFs, significantly impacts the sensitivity of cancer cells to anti-cancer drugs, contributing to tumor progression and resistance to both chemotherapy and immunotherapy. Therefore, targeting CAFs and the ECM may enhance the effectiveness of therapies like FOLFIRINOX. This study aimed to develop a novel oncolytic virotherapy for treatment-resistant pancreatic cancer.

Materials and methods: In the first screening assay, we found that coxsackievirus B3 (CVB3) exhibited potent oncolytic activity. We examined whether CVB3 has oncolytic effects on human pancreatic cancer cells in vitro, and whether it has oncolytic activity against cancer-associated fibroblasts (CAFs) in pancreatic cancer.

Results: CVB3 demonstrated potent oncolytic effects in two out of three pancreatic cancer cell lines tested. Additionally, CVB3 demonstrated a cell-killing effect on CAFs, indicating its dual activity against both pancreatic cancer cells and the supportive stromal environment.

Conclusion: CVB3 shows promise as an oncolytic virus effective against pancreatic cancer cells and CAFs, suggesting its potential as a novel virotherapy for pancreatic cancer. These findings highlight CVB3 as a candidate for further development as a therapeutic modality aimed at improving drug sensitivity and patient prognosis in pancreatic cancer.