Figure 5.

Combination anti-CTLA-4 or anti-PD-L1 plus multi-dose TNF-armed MYXV/PBMC virotherapy leads to long-term survival compared to monotherapies

(A) Diagram of experimental setup. BALB/c mice were inoculated with K7M2-Luc cells at day 0 via i.v. injection. Treatment with ICIs started at day 1 after tumor inoculation and continued every third day for four total doses. Treatment with vMyx-hTNF (MYXV-TNF) using PBMC carrier cells started at 3 days post-inoculation and continued every fourth day for four total doses. Animals were then followed for 120 days. (B) Kaplan-Meier survival curves comparing monotherapy with multi-dose vMyx-hTNF/PBMCs (n = 10), anti-PD-L1 (n = 8), and combinations of anti-PD-L1/anti-CTLA-4 (n = 10), vMyx-hTNF/anti-PD-L1 (n = 6), and vMyx-hTNF/anti-CTLA-4 (n = 7). All therapies led to a significant survival increase compared to untreated controls (n = 8). Combination of vMyx-hTNF/PBMCs plus either anti-PD-L1 or anti-CTLA-4 increased mean survival and generated long-term survivors, as compared to vMyx-hTNF/PBMC or ICI monotherapies. (C) Representative tumor luminescence images at 17 weeks (119 days) after tumor inoculation showing animals treated with (i) vMyx-hTNF/PBMCs plus anti-PD-L1 and (ii) vMyx-hTNF/PBMCs plus anti-CTLA-4. These animals were tumor-free at the study end date of 120 days.