Unknown

Dataset Information

0

Oncolytic herpes simplex virus infects myeloma cells in vitro and in vivo


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. Graphical Abstract Receptors of oncolytic herpes simplex virus (oHSV-1), NECTIN-1, and HVEM are expressed on multiple myeloma (MM) cells. Whereas NECTIN-1 expression is variable among MM cells, HVEM is ubiquitously and highly expressed on all samples tested. However, no viral replication occurred. Instead, oHSV-1 induced MM cell apoptosis via caspase-3 cleavage.

SUBMITTER: Ghose J 

PROVIDER: S-EPMC7940704 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC2835221 | biostudies-other
| S-EPMC8235327 | biostudies-literature
| S-EPMC5021410 | biostudies-literature
2022-08-02 | GSE210178 | GEO
| S-EPMC5836060 | biostudies-literature
| S-EPMC4859661 | biostudies-literature
| S-EPMC7664223 | biostudies-literature
| S-EPMC4326267 | biostudies-literature
| S-EPMC5435599 | biostudies-literature