Oncolytic α-herpesvirus and myeloid-tropic cytomegalovirus cooperatively enhance systemic antitumor responses

Oncolytic varicella-zoster virus engineered with ORF8 deletion and armed with drug-controllable interleukin-12

“…The experiment included the HSV-1 KOS-ΔICP34.5ΔICP47-gBsyn-scIL12 virus, characterized by its hyperfusogenic gB and scIL12 expression along with the absence of both ICP34.5 and ICP47, as a comparative control. 38 When given in equal doses (1×10 5 plaque-forming units (PFUs) per injection), the Ellen-ΔORF8-tet-off-scIL12 virus exhibited better overall antitumor efficacy in comparison to the KOS-ΔICP34.5ΔICP47-gBsyn-scIL12 virus ( figure 6C,D ). After being injected, the oncolytic HSV derived from KOS may cause the lysis of target cells and was then rapidly cleared by the immune system.…”

“…After being injected, the oncolytic HSV derived from KOS may cause the lysis of target cells and was then rapidly cleared by the immune system. 38 No treatmentrelated toxicity was observed across all treatment groups (figure 6D,E).…”

“…The HSV-1 KOS-ΔICP34.5ΔICP47-gBsyn-scIL12 virus was grown in Vero cells and purified with the method as described previously. 38 …”

“…B16-F10-nectin1 cells were constructed to stably express the human nectin1 and support HSV-1 replication. 38 The SH-SY5Y cells (CRL-2266, ATCC) were cultured in DMEM/F12 Medium with 100 units/mL of penicillin/streptomycin and 10% FBS. Differentiated human neuronal dSH-SY5Y cells were obtained by culturing SH-SY5Y cells in DMEM/F12 medium containing 2% FBS and 10 µM retinoic acid (R2625, Sigma) for 3 days followed by a 5-day differentiation in DMEM/F12 medium supplemented with 100 ng/mL beta-nerve growth factor (788506, Biolegend) and 50 ng/mL brain-derived neurotrophic factor (788904, Biolegend).…”