Novel chimeric parapoxvirus CF189 as an oncolytic immunotherapy in triple-negative breast cancer

Triple-negative breast cancer is an aggressive subtype of breast cancer with high recurrence rate and poor prognosis. Here we describe a novel, genetically engineered parapoxvirus that efficiently kills triple-negative breast cancer. A novel chimeric parapoxvirus (CF189) was generated via homologous...

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Bibliographic Details
Published in:Surgery 2018-02, Vol.163 (2), p.336-342
Main Authors: Choi, Audrey H., O'Leary, Michael P., Chaurasiya, Shyambabu, Lu, Jianming, Kim, Sang-In, Fong, Yuman, Chen, Nanhai G.
Format: Article
Language:English
Subjects:
Animals
Cell Line, Tumor
Humans
Immunotherapy
Killer Cells, Natural - physiology
Mice, Nude
Oncolytic Virotherapy
Parapoxvirus
Triple Negative Breast Neoplasms - therapy
Xenograft Model Antitumor Assays
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Summary:Triple-negative breast cancer is an aggressive subtype of breast cancer with high recurrence rate and poor prognosis. Here we describe a novel, genetically engineered parapoxvirus that efficiently kills triple-negative breast cancer. A novel chimeric parapoxvirus (CF189) was generated via homologous recombination and identified through high-throughput screening. Cytotoxicity was assayed in vitro in 4 triple-negative breast cancer cell lines. Viral replication was examined through standard plaque assay. Orthotopic triple-negative breast cancer xenografts were generated by MDA-MB-468 implantation into the 2nd and 4th mammary fat pads of athymic nude mice and treated with the virus. Chimeric parapoxvirus (CF189) demonstrated dose-dependent cytotoxicity at low multiplicity of infection, with > 80% cell death 6 days after treatment. Significant reductions in tumor size were observed 2 weeks after intratumoral injection at doses as low as 103 plaque-forming units (PFU) compared with control (P 
ISSN:0039-6060
1532-7361
DOI:10.1016/j.surg.2017.09.030