An Adjuvanted WT1 Vaccine Delivered after Oncovirotherapy and FL Treatment Combination Generates WT1-Specific CD8+ TILs and Requires Batf3-Driven CD103+ DCs
(A) Graphical timeline of the treatment scheme in ID8-T tumor-bearing mice. C57BL/6 mice were injected i.p. with 3 × 105 ID8-T cells. Treatment with OVV or OVV-CXCR4-A (108 PFU delivered i.p.) was initiated 10 days later. To expand CD103+ DCs, FL was injected i.p. at 5 μg/injection for 4 consecutive days, beginning on day 8 after virotherapy treatment. The WT1-specific peptide was delivered i.p. (50 μg/injection) with poly(I:C) (p(I:C); 50 μg/injection) on day 3 after the last FL delivery. (B) Survival of ID8-T tumor-bearing mice (n = 5–10 mice/group) after WT1 immunization of OVV- and OVV plus FL-treated mice. Kaplan-Meier survival plots were prepared, and significance was determined using the log rank method. **p < 0.01. (C and D) Representative flow cytometry staining (C) and relative proportions of WT1 tetramer+CD8+ TILs (D) after combined treatment of OVV and WT1 vaccine as well as OVV and FL treatment followed by WT1 vaccination (n = 4–5 mice/group). (E) Survival of ID8-T tumor-bearing mice (n = 5–10 mice/group) after WT1 immunization of OVV-CXCR4-A and OVV-CXCR4-A plus FL-treated mice. *p < 0.05, ***p < 0.001. (F and G) Representative flow cytometry staining (F) and relative proportions of WT1 tetramer+CD8+ TILs (G) after combined treatment of OVV-CXCR4-A and WT1 vaccine and OVV-CXCR4-A plus FL treatment followed by WT1 vaccination (n = 4–5 mice/group). (H) Survival of ID8-T tumor-bearing Batf3−/− female mice (n = 5) after treatment with OVV-CXCR4-A alone or in combination with FL and the WT1 adjuvanted vaccine. Kaplan-Meier survival plots were prepared, and significance was determined using the log rank method. ***p < 0.001.