Related Experiment Video
Updated: Apr 25, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Assessment of oncolytic HSV efficacy following increased entry-receptor expression in malignant peripheral nerve
J D Jackson1, A M McMorris1, J C Roth2
1Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Abstract:
Limited expression and distribution of nectin-1, the major herpes simplex virus (HSV) type-1 entry-receptor, within tumors has been proposed as an impediment to oncolytic HSV (oHSV) therapy. To determine whether resistance to oHSVs in malignant peripheral nerve sheath tumors (MPNSTs) was explained by this hypothesis, nectin-1 expression and oHSV viral yields were assessed in a panel of MPNST cell lines using γ134.5-attenuated (Δγ134.5) oHSVs and a γ134.5 wild-type (wt) virus for comparison. Although there was a correlation between nectin-1 levels and viral yields with the wt virus (R=0.75, P =0.03), there was no correlation for Δγ134.5 viruses (G207, R7020 or C101) and a modest trend for the second-generation oHSV C134 (R=0.62, P=0.10). Nectin-1 overexpression in resistant MPNST cell lines did not improve Δγ134.5 oHSV output. While multistep replication assays showed that nectin-1 overexpression improved Δγ134.5 oHSV cell-to-cell spread, it did not confer a sensitive phenotype to resistant cells. Finally, oHSV yields were not improved with increased nectin-1 in vivo. We conclude that nectin-1 expression is not the primary obstacle of productive infection for Δγ134.5 oHSVs in MPNST cell lines. In contrast, viruses that are competent in their ability to counter the antiviral response may derive benefit with higher nectin-1 expression.
Insights
Nectin-1 expression is not the main barrier for oncolytic herpes simplex virus (oHSV) therapy in malignant peripheral nerve sheath tumors. Other factors, like the virus's ability to overcome antiviral responses, are more critical for oHSV efficacy.
Area of Science:
- Oncolytic virotherapy
- Cancer research
- Virology
Background:
- Oncolytic herpes simplex virus (oHSV) therapy shows promise for cancer treatment.
- Limited expression of nectin-1, a key HSV entry receptor, in tumors is a proposed barrier to oHSV efficacy.
- Malignant peripheral nerve sheath tumors (MPNSTs) are a challenging cancer type for oHSV treatment.
Purpose of the Study:
- To investigate if nectin-1 expression levels explain the resistance of MPNSTs to oHSV therapy.
- To assess the role of nectin-1 in oHSV infection and replication within MPNSTs.
Main Methods:
- Assessed nectin-1 expression and oHSV viral yields in MPNST cell lines.
- Utilized γ134.5-attenuated (Δγ134.5) oHSVs and a γ134.5 wild-type (wt) virus.
- Performed nectin-1 overexpression experiments and multistep replication assays.
- Evaluated oHSV yields in vivo.
Main Results:
- A correlation between nectin-1 levels and viral yields was observed for the wt virus, but not for Δγ134.5 oHSVs.
- Nectin-1 overexpression did not enhance Δγ134.5 oHSV output in resistant MPNST cell lines.
- While nectin-1 improved cell-to-cell spread of Δγ134.5 oHSVs, it did not overcome resistance.
- Increased nectin-1 did not improve oHSV yields in vivo.
Conclusions:
- Nectin-1 expression is not the primary obstacle for productive infection by Δγ134.5 oHSVs in MPNST cell lines.
- The virus's ability to counteract the host's antiviral response is likely more important for oHSV efficacy in MPNSTs.
- Further research should focus on viral mechanisms that overcome tumor-specific antiviral defenses for improved oHSV therapy.
