Related Experiment Video
Updated: Dec 15, 2025
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Bovine pestivirus is a new alternative virus for multiple myeloma oncolytic virotherapy
Valentina Marchica1, Valentina Franceschi2, Rosanna Vescovini1
1Department of Medicine and Surgery, University of Parma, Parma, Italy.
Background:
The oncolytic viruses have shown promising results for the treatment of multiple myeloma. However, the use of human viruses is limited by the patients' antiviral immune response. In this study, we investigated an alternative oncolytic strategy using non-human pathogen viruses as the bovine viral diarrhea virus (BVDV) that were able to interact with CD46.
Methods:
We treated several human myeloma cell lines and non-myeloma cell lines with BVDV to evaluate the expression of CD46 and to study the effect on cell viability by flow cytometry. The possible synergistic effect of bortezomib in combination with BVDV was also tested. Moreover, we infected the bone marrow mononuclear cells obtained from myeloma patients and we checked the BVDV effect on different cell populations, defined by CD138, CD14, CD3, CD19, and CD56 expression evaluated by flow cytometry. Finally, the in vivo BVDV effect was tested in NOD-SCID mice injected subcutaneously with myeloma cell lines.
Results:
Human myeloma cells were selectively sensitive to BVDV treatment with an increase of cell death and, consequently, of apoptotic markers. Consistently, bone marrow mononuclear cells isolated from myeloma patients treated with BVDV, showed a significant selective decrease of the percentage of viable CD138+ cells. Interestingly, bortezomib pre-treatment significantly increased the cytotoxic effect of BVDV in myeloma cell lines with a synergistic effect. Finally, the in vitro data were confirmed in an in vivo myeloma mouse model showing that BVDV treatment significantly reduced the tumoral burden compared to the vehicle.
Conclusions:
Overall, our data indicate, for the first time, a direct oncolytic effect of the BVDV in human myeloma cells suggesting its possible use as novel alternative anti-myeloma virotherapy strategy.
Insights
Bovine viral diarrhea virus (BVDV) shows direct oncolytic effects against multiple myeloma cells. This non-human virus offers a promising alternative virotherapy strategy, even showing synergy with bortezomib.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Oncolytic viruses show promise for multiple myeloma treatment.
- Patient antiviral responses limit human virus efficacy.
- Investigated non-human bovine viral diarrhea virus (BVDV) for CD46 interaction.
Purpose of the Study:
- Evaluate BVDV's oncolytic potential against human myeloma cells.
- Assess BVDV's effect on myeloma patient bone marrow cells.
- Determine synergistic effects with bortezomib and in vivo efficacy.
Main Methods:
- Treated myeloma cell lines with BVDV, assessing CD46 expression and viability via flow cytometry.
- Tested BVDV in combination with bortezomib.
- Analyzed BVDV effects on patient bone marrow mononuclear cells (BM-MNCs).
- Evaluated in vivo efficacy in a mouse model.
Main Results:
- BVDV selectively induced cell death and apoptosis in human myeloma cells.
- BVDV significantly reduced viable CD138+ cells in patient BM-MNCs.
- Bortezomib enhanced BVDV's cytotoxic effect synergistically.
- In vivo studies confirmed reduced tumor burden with BVDV treatment.
Conclusions:
- BVDV demonstrates a direct oncolytic effect on human myeloma cells.
- BVDV represents a novel alternative virotherapy strategy for multiple myeloma.
- The findings support further investigation of BVDV for myeloma treatment.
Related Concept Videos
01:03Rous Sarcoma Virus (RSV) and Cancer
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
01:29Subviral Agents
01:27Tumor Immunotherapy