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

• Published in: Surgery Vol. 163; no. 2; pp. 336 - 342
• Main Authors: Choi, Audrey H., O'Leary, Michael P., Chaurasiya, Shyambabu, Lu, Jianming, Kim, Sang-In, Fong, Yuman, Chen, Nanhai G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2018
• 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
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1016/j.surg.2017.09.030

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 < 0.01). In addition, abscopal effect (shrinkage of noninjected remote tumors) was clearly demonstrated. Chimeric parapoxvirus (CF189) demonstrated efficient cytotoxicity in vitro and potent antitumor effect in vivo at doses as low as 103 PFU. These are data encouraging of clinical development for this highly potent agent against triple-negative breast cancer.