Related Experiment Video
Updated: Nov 12, 2025
Growth, Purification, and Titration of Oncolytic Herpes Simplex Virus
Published on: May 13, 2021
Oncolytic herpes simplex virus infects myeloma cells in vitro and in vivo
Jayeeta Ghose1, Ada Dona2, Mariam Murtadha2
1Department of Radiation Oncology, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Abstract:
Because most patients with multiple myeloma (MM) develop resistance to current regimens, novel approaches are needed. Genetically modified, replication-competent oncolytic viruses exhibit high tropism for tumor cells regardless of cancer stage and prior treatment. Receptors of oncolytic herpes simplex virus 1 (oHSV-1), NECTIN-1, and HVEM are expressed on MM cells, prompting us to investigate the use of oHSV-1 against MM. Using oHSV-1-expressing GFP, we found a dose-dependent increase in the GFP+ signal in MM cell lines and primary MM cells. Whereas NECTIN-1 expression is variable among MM cells, we discovered that HVEM is ubiquitously and highly expressed on all samples tested. Expression of HVEM was consistently higher on CD138+/CD38+ plasma cells than in non-plasma cells. HVEM blocking demonstrated the requirement of this receptor for infection. However, we observed that, although oHSV-1 could efficiently infect and kill all MM cell lines tested, no viral replication occurred. Instead, we identified that oHSV-1 induced MM cell apoptosis via caspase-3 cleavage. We further noted that oHSV-1 yielded a significant decrease in tumor volume in two mouse xenograft models. Therefore, oHSV-1 warrants exploration as a novel potentially effective treatment option in MM, and HVEM should be investigated as a possible therapeutic target.
Insights
Oncolytic herpes simplex virus 1 (oHSV-1) effectively targets multiple myeloma (MM) cells by inducing apoptosis, not replication. This virus shows promise as a novel MM treatment, with HVEM identified as a key therapeutic target.
Area of Science:
- Oncolytic virotherapy
- Cancer biology
- Immunology
Background:
- Multiple myeloma (MM) often develops resistance to existing therapies, necessitating novel treatment strategies.
- Oncolytic viruses, such as oncolytic herpes simplex virus 1 (oHSV-1), demonstrate tumor cell tropism and potential therapeutic value.
- Key receptors for oHSV-1, NECTIN-1 and HVEM, are expressed on MM cells, suggesting oHSV-1 as a potential MM treatment.
Purpose of the Study:
- To investigate the efficacy of oHSV-1 as a treatment for multiple myeloma (MM).
- To identify the viral entry mechanism and cellular effects of oHSV-1 in MM.
- To evaluate HVEM as a potential therapeutic target in MM.
Main Methods:
- oHSV-1 expressing GFP was used to assess infection in MM cell lines and primary cells.
- Expression levels of NECTIN-1 and HVEM were analyzed on MM cells.
- HVEM blocking experiments were performed to determine its role in oHSV-1 infection.
- Viral replication and MM cell apoptosis were measured.
- Efficacy was evaluated in mouse xenograft models of MM.
Main Results:
- oHSV-1 infection of MM cells resulted in a dose-dependent increase in GFP expression.
- HVEM was ubiquitously and highly expressed on all tested MM samples, particularly on plasma cells.
- HVEM is essential for oHSV-1 infection of MM cells.
- oHSV-1 induced MM cell apoptosis via caspase-3 cleavage without viral replication.
- oHSV-1 significantly reduced tumor volume in mouse xenograft models.
Conclusions:
- oHSV-1 demonstrates significant anti-MM activity by inducing apoptosis.
- HVEM is a crucial receptor for oHSV-1 entry into MM cells and a potential therapeutic target.
- oHSV-1 represents a promising novel therapeutic approach for multiple myeloma.
