Abstract
Oncolytic viruses have shown excellent safety profiles in preclinical and clinical studies; however, in most cases therapeutic benefits have been modest. We have previously reported the generation of a chimeric poxvirus (CF33), with significantly improved oncolytic characteristics, through chimerization among different poxviruses. Here we report the sequence analysis of CF33 and oncolytic potential of a GFP-encoding CF33 virus (CF33-GFP) with a J2R deletion in lung cancer models. Replication of CF33-GFP and the resulting cytotoxicity were higher in cancer cell lines compared to a normal cell line, in vitro. After infection with virus, cancer cells expressed markers for immunogenic cell death in vitro. Furthermore, CF33-GFP was safe and exerted potent anti-tumor effects at a dose as low as 1000 plaque forming units in both virus-injected and un-injected distant tumors in A549 tumor xenograft model in mice. Likewise, in a syngeneic model of lung cancer in mice, the virus showed significant anti-tumor effect and was found to increase tumor infiltration by CD8+ T cells. Collectively, these data warrant further investigation of this novel chimeric poxvirus for its potential use as a cancer bio-therapeutic.
Highlights
Lung cancer is the second most common cancer type in both men and women [1]
We previously reported the construction of a chimeric poxvirus (CF33), with enhanced anti-tumor activity, through chimerization among 9 species of orthopoxvirus including multiple strains of vaccinia virus (VACV) [20, 21]
We have previously reported the construction of a chimeric poxvirus CF33 that is more efficient in killing cancer cells than the parental poxviruses [20, 21]
Summary
Lung cancer is the second most common cancer type in both men and women [1]. Despite advancements in diagnosis and treatment lung cancer remains the leading cause of cancer mortality worldwide [2]. Surgery is the first line therapy whereas for advanced, unresectable disease a combination of chemo- and radiation is commonly used [3,4,5]. Rate of recurrence after initial remission is high for lung cancer and 5-year survival is dismal at 18% [1]. Alternative therapeutics need to be developed for better treatment of lung cancer.
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