A Novel Human Cell-Based Spheroid Model to Screen for Oncolytic Viruses and Oncolytic Viral Proteins

Abstract

Colorectal cancer is one of the major causes of cancer-related deaths worldwide and surgery has been the ideal treatment method. Oncolytic virus therapy uses a modified virus to specifically kill only cancer cells without harming the neighboring non-cancerous cells. A best example is Newcastle Disease Virus (NDV), an avian paramyxovirus which is seen as a promising oncolytic virus shown to combat many different types of cancers by in vitro and few in vivo animal studies. Traditionally, anticancer screening is done through in vitro cell line based assays in the lab and promising candidates are further tested in animal tumor models which is more expensive, time consuming and may not always reflect the truth due to species variations. Further results from the in vitro cell culture system may not always predict the outcome in animal models. 3D cell based models, i.e. spheroids are better than the cell lines as they can mimic the microenvironment of a tumor and can be used as an alternative to animal testing. In this study we demonstrated a novel human colorectal cancer spheroid model, which mimics the tumor microenvironment and better emulates the pathophysiology of human colorectal cancer, as a tool for identification of oncolytic agents. Through cytotoxic and colony forming assays we show the potential application of the spheroid model as a high throughput enabled anticancer screen.