A novel Vaccinia virus enhances anti-tumor efficacy and promotes long-term anti-tumor response in a murine model of colorectal cancer

Abstract Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world and there still remains an urgent need to develop long-lasting therapies to treat CRC and prevent recurrence in patients. Oncolytic virus therapy (OVT) has demonstrated remarkable efficacy in a number of different cancer models. Here we report a novel Vaccinia virus (VV)-based OVT for treatment of CRC. The novel VV, based on the recently reported novel VVLΔTKΔN1L virus, was armed with the pleiotropic cytokine interleukin-21 (IL-21) to enhance anti-tumor immune responses stimulated after viral infection of tumor cells. Compared with unarmed virus, VVLΔTKΔN1L-mIL21 had a superior anti-tumor efficacy in murine CMT93 subcutaneous colorectal cancer models in vivo, mediated mainly by CD8+ T cells. Treatment resulted in development of long-term immunity against CMT93 tumor cells as evidenced by prevention of disease recurrence. These results demonstrate that VVLΔTKΔN1L-mIL21 is a promising therapeutic agent for treatment of CRC.