Bovine pestivirus is a new alternative virus for multiple myeloma oncolytic virotherapy

Valentina Marchica, Valentina Franceschi, Rosanna Vescovini, Paola Storti, Emanuela Vicario, Denise Toscani, Alessia Zorzoli, Irma Airoldi, Benedetta Dalla Palma, Nicoletta Campanini, Eugenia Martella, Cristina Mancini, Federica Costa, Gaetano Donofrio, Nicola Giuliani

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)89
JournalJournal of hematology & oncology
Volume13
Issue number1
DOIs
Publication statusPublished - Jul 11 2020

Fingerprint Dive into the research topics of 'Bovine pestivirus is a new alternative virus for multiple myeloma oncolytic virotherapy'. Together they form a unique fingerprint.

Cite this