Bovine herpesvirus type 1 (BoHV-1) effectively targets and lyses multiple myeloma (MM) cells while remaining nonpathogenic to humans, bypassing the obstacle of pre-existing antiviral immunity.
The virus induces direct oncolysis via mitochondrial apoptosis and the suppression of critical pro-survival metabolic pathways, including MYC signaling and the unfolded protein response (UPR).
BoHV-1 therapy triggers a profound shift in the bone marrow microenvironment, converting immunosuppressive myeloid cells into pro-inflammatory M1-like phenotypes and activating CD8+ T and NK cells.
Synergistic effects were observed when combining BoHV-1 with bortezomib, lenalidomide, and daratumumab, the latter driven by virus-induced CD38 upregulation.
