Oncolytic poxvirus CF33-hNIS-ΔF14.5 favorably modulates tumor immune microenvironment and works synergistically with anti-PD-L1 antibody in a triple-negative breast cancer model.

Oncoimmunology
Shyambabu ChaurasiyaYuman Fong

Abstract

Triple-negative breast cancer is the most aggressive subtype of breast cancer and is difficult to treat. Breast cancer is considered to be poorly immunogenic and hence is less responsive to immunotherapies. We tested whether the oncolytic poxvirus CF33-hNIS-ΔF14.5 could modulate tumor immune microenvironment and make the tumors responsive to the immune checkpoint inhibitor anti-PD-L1. We found that virus infection causes the upregulation of PD-L1 levels on triple-negative breast cancer cells in vitro as well as in vivo in mice. In a mouse model of orthotopic triple-negative breast cancer, the virus was found to increase tumor infiltration by CD8+ T cells. Likewise, in mice treated with CF33-hNIS-ΔF14.5 high levels of proinflammatory cytokines IFNγ and IL-6 were found in the tumors but not in the serum. The levels of immune modulation were even higher in mice that were treated with a combination of the virus and anti-PD-L1 antibody. While CF33-hNIS-ΔF14.5 and anti-PD-L1 antibody failed to exert significant anti-tumor effect as a single agent, a combination of the two agents resulted in significant anti-tumor effect with 50% mice experiencing complete tumor regression when both agents were injected intra-tumorally. Furthermore, t...Continue Reading

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Citations

Oct 8, 2020·International Journal of Molecular Sciences·Sang-In KimSusanne G Warner
Dec 4, 2020·Cancer Gene Therapy·Shyambabu Chaurasiya, Yuman Fong
Mar 9, 2021·Frontiers in Veterinary Science·Guillermo ValdiviaLaura Peña
Aug 10, 2021·Frontiers in Microbiology·Yaqi ZhaoBin Xu

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Methods Mentioned

BETA
FACS
flowcytometry
xenograft

Software Mentioned

GraphPad Prism
Stats
FlowJo
LegendPlex
QuPath

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