A novel vaccinia virus enhances anti-tumor efficacy and promotes a long-term anti-tumor response in a murine model of colorectal cancer
View/ Open
Volume
20
Pagination
71 - 81
Publisher
Publisher URL
DOI
10.1016/j.omto.2020.11.002
Journal
MOLECULAR THERAPY-ONCOLYTICS
ISSN
2372-7705
Metadata
Show full item recordAbstract
Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world, and there 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 VVLDTKDN1L 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 an unarmed virus,
VVLDTKDN1L-mIL-21 had a superior anti-tumor efficacy in
murine CMT93 subcutaneous CRC 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 VVLDTKDN1L-mIL-21 is a promising therapeutic agent for treatment of CRC.