Abstract
Vaccinia virus, a member of the Poxviridae family, has been extensively used as an oncolytic agent and has entered late stage clinical development. In this study, we evaluated the potential oncolytic properties of other members of the Poxviridae family. Numerous tumor cell lines were infected with ten non-vaccinia poxviruses to identify which virus displayed the most potential as an oncolytic agent. Cell viability indicated that tumor cell lines were differentially susceptible to each virus. Raccoonpox virus was the most potent of the tested poxviruses and was highly effective in controlling cell growth in all tumor cell lines. To investigate further the oncolytic capacity of the Raccoonpox virus, we have generated a thymidine kinase (TK)-deleted recombinant Raccoonpox virus expressing the suicide gene FCU1. This TK-deleted Raccoonpox virus was notably attenuated in normal primary cells but replicated efficiently in numerous tumor cell lines. In human colon cancer xenograft model, a single intratumoral inoculation of the recombinant Raccoonpox virus, in combination with 5-fluorocytosine administration, produced relevant tumor growth control. The results demonstrated significant antitumoral activity of this new modified Raccoonpox virus armed with FCU1 and this virus could be considered to be included into the growing armamentarium of oncolytic virotherapy for cancer.
Highlights
Oncolytic virotherapy for cancer treatment utilizes naturally occurring or engineered viruses for selective infection and cancer cell death without any adverse effect on normal cells
The results demonstrated significant antitumoral activity of this new modified Raccoonpox virus armed with FCU1 and this virus could be considered to be included into the growing armamentarium of oncolytic virotherapy for cancer
Oncolytic activity of the ten poxviruses and progeny virion production of poxviruses To evaluate the relative ability of the different poxviruses to control the growth of tumor cells, the ED50 of the 10 poxviruses was assessed on a panel of cancer cell lines of different origins (Figure 1A)
Summary
Oncolytic virotherapy for cancer treatment utilizes naturally occurring or engineered viruses for selective infection and cancer cell death without any adverse effect on normal cells. Its potency to preferentially infect and kill cancer cells has been proven for many years and advanced clinical trials are ongoing to evaluate this virus in human [1]. The Wyeth based vector Pexa-Vec (JX-594) has shown efficacy in hepatocarcinoma (HCC) [1] and a Phase 3 study is ongoing in primary HCC (National Clinical Trial NCT02562755). The TK-deleted VACV can selectively infect tumor tissues, whereas in most normal cells, deletion of the TK gene greatly reduces the virus replication [8]
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