*4.1. Cyclophosphamide (CP)*

CP was extensively tested in combination with OVs, where synergy was described mostly through CPs immunosuppressive effects which allowed the OVs to replicate longer, thereby prolonging and enhancing their therapeutic efficacy [238–241]. However, CP can also play a role in improving the anti-tumor immune response elicited by initial OV treatment. Low-dose CP does not have the same immunosuppressive and toxic effects that allow increased OV replication, but does decrease the number of Tregs without compromising induction of antitumor or antiviral T-cell responses [242,243]. This selective sensitivity of Tregs to CP, comprehensively reviewed by Madondo et al. [244], works through several mechanisms. Combined, these mechanisms allow for depletion or reduced activity of Tregs, while leaving other cell populations intact [244]. This approach shows great promise, especially in combination with oncolytic virus-based cancer vaccination [245].
