| Autor: |
Jayeeta Ghose, Ada Dona, Mariam Murtadha, Emine Gulsen Gunes, Enrico Caserta, Ji Young Yoo, Luke Russell, Alena Cristina Jaime-Ramirez, Benjamin G. Barwick, Vikas A. Gupta, James F. Sanchez, Douglas W. Sborov, Steven T. Rosen, Amrita Krishnan, Lawrence H. Boise, Balveen Kaur, Craig C. Hofmeister, Flavia Pichiorri |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Oncolytics, Vol 20, Iss , Pp 519-531 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2372-7705 |
| DOI: |
10.1016/j.omto.2021.02.009 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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