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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Novel chimeric parapoxvirus CF189 as an oncolytic immunotherapy in triple-negative breast cancer
Audrey H Choi1, Michael P O'Leary1, Shyambabu Chaurasiya1
1Department of Surgery, City of Hope National Medical Center, Duarte, CA.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
A novel chimeric parapoxvirus (CF189) effectively kills triple-negative breast cancer cells in vitro and reduces tumor size in vivo. This virus shows promise as a potent new treatment for triple-negative breast cancer.
Area of Science:
- Virology
- Oncology
- Biotechnology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis.
- Novel therapeutic strategies are urgently needed for TNBC.
- Genetically engineered viruses offer a promising avenue for cancer treatment.
Purpose of the Study:
- To develop and evaluate a novel, genetically engineered parapoxvirus for its efficacy against triple-negative breast cancer.
- To assess the in vitro and in vivo antitumor activity of the chimeric parapoxvirus CF189.
Main Methods:
- A chimeric parapoxvirus (CF189) was engineered and selected using high-throughput screening.
- In vitro cytotoxicity was assessed in TNBC cell lines.
- In vivo efficacy was evaluated in orthotopic TNBC xenograft mouse models.
Main Results:
- CF189 demonstrated dose-dependent cytotoxicity, causing over 80% cell death in TNBC cell lines.
- Intratumoral injection of CF189 significantly reduced tumor size in vivo at low doses (10^3 PFU).
- An abscopal effect, shrinkage of remote tumors, was observed.
Conclusions:
- The chimeric parapoxvirus CF189 exhibits potent in vitro and in vivo antitumor activity against triple-negative breast cancer.
- CF189 demonstrates significant potential for clinical development as a novel therapeutic agent for TNBC.
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