Bovine Pestivirus: Novel Oncolytic Virotherapy Under Study in Myeloma
Posted: Monday, September 21, 2020
Oncolytic virotherapy has demonstrated efficacy against multiple myeloma, for which the measles virus is the most well studied. However, the use of human viruses has been limited by a patient’s own immune response. Nicola Giuliani, MD, PhD, of the University of Parma, Italy, and colleagues investigated the use of the bovine viral diarrhea virus (BVDV) as an alternative in the treatment of multiple myeloma. BVDV enters cells by binding CD46, similar to the measles virus, and seems to have a direct oncolytic effect in human myeloma cells. These study results, published in the Journal of Hematology & Oncology, may provide a rationale to design a clinical approach to the use of BVDV in this patient population.
Researchers treated several human myeloma cell lines and nonmyeloma human cells with BVDV and cultured for 24, 48, and 72 hours. Flow-cytometry results showed that human myeloma cells treated with BVDV had significantly higher mortality than nonmyeloma cells. They also found that although BVDV was able to bind both multiple myeloma cell lines and nonmyeloma cells, the virotherapy was only able to enter myeloma cells.
Next, the researchers analyzed the expression of apoptotic markers. Human myeloma cells treated with BVDV were found to have had a significant increase in apoptosis after 48 and 72 hours of infection compared with controls. Prior research showed enhanced cytotoxic in vitro effect when multiple myeloma cells and other tumor models were pretreated with bortezomib before oncolytic virotherapy; bortezomib-induced apoptosis due to activation of the same apoptotic pathway as BVDV. After pretreatment with bortezomib, researchers observed a statistically significant decrease in cell viability after 24 and 48 hours, but the highest mortality rates occurred after 72 hours. The combination of bortezomib and BVDV synergistically killed myeloma cells.
Disclosure: For full disclosures of the study authors, visit biomedcentral.com.