Fig. 2.

The potential dual role of the oncolytic MYXV in the setting of allo-HSCT. The oncolytic virus MYXV can bind efficiently to resting human T cells but the virus infection halts at this early stage. However, following activation of T cells via α-CD3/CD28 stimuli or by contact with an alloantigen, these activated cells now launch the full virus infection cycle and become virus-bearing “carrier cells.” The productive infection of activated T cells also impairs T cell functions including their capacity to proliferate and downregulates the expression of at least some of their GvHD-promoting effector cytokines. For example, activated human T cells infected with MYXV produce lower levels of IL-2, IL2-R-α, and IFN-γ, which are part of the hallmark of GvHD. In a related scenario, when MYXV-infected/activated human T cells are co-cultured with human MM U266 cancer cell line, the virus (either parental or progeny) can be transferred to these cancer cells via cell-cell contact. Once contacted, the myeloma cells are eliminated via GvT (graft-vs-tumor) and/or VvT (virus-vs-tumor), or a combination of both