*3.4. ONCR-177*

ONCR-177 (by Oncorus Inc. Cambridge, MA, USA) is a recombinant HSV-1 virus construct that is a derivative of ONCR-159 [54], which contains a *UL37* and *ICP47* mutation and 4 miR-T cassettes that were inserted into the gene regions of *ICP4*, *ICp27*, *UL8* and γ*34.5*, thereby diminishing viral replication and mitigating reduced neurovirulence and also resistance to shut down by host interferon responses [55]. Based on this, the authors state that ONCR-177 has been further modified by expression for IL-12, CCL4, FLT3LG, and blocking antibody sequences for CTLA-4 and PD-1 to increase NKand T-cell activation, dendritic cell availability, and antagonize T-cell exhaustion [54]. ONCR-177 monotherapy as well as combined treatment with pembrolizumab is being tested for the maximum tolerated dose and preliminary efficacy in advanced and metastatic solid cancers in a phase I study (NCT04348916).
