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

Abstract

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.