Fig. 7: RT3D plus talazoparib enhances anti-tumour efficacy which correlates with an increase in immune response.
A Treatment schedule, black/6 mice carrying 4434 tumours were treated with oral administration of 0.1 mg/kg talazoparib or vehicle from Day 1–5. RT3D was injected intratumorally on Day 3 at 1 × 106 pfu or sham injection. B Size of tumours were measured for each treatment cohort consisting of vehicle (10% DMAc, 6% Solutol and 84% PBS), 0.1 mg/kg talazoparib, 1 × 106 pfu RT3D or combination. Each bar represents mean SEM ± for each treatment group. C Kaplan–Meier curve was evaluated for each treatment group to assess the median survival rate. For (B and C), vehicle n = 6, RT3D n = 6, talazoparib n = 6 and combination n = 6 animals per group. D Mice cured at day 90 following talazoparib alone (2/6), RT3D alone (2/6) or RT3D plus talazoparib (6/6) were rechallenged on the other flank and compared with naïve mice injected with 4434 tumours (both implanted at 4 × 106 cells) and tumor growth assessed. Control n = 6, RT3D n = 2, talazoparib n = 2 and combination n = 6 animals per group. E Deconvolution of immune cells in 4434 tumours following RT3D and talazoparib treatment. Tumours were dissected on day 8 (3 mice per group) after treatment, total RNA was isolated and gene expression analysis performed using the mouse Immunology Profiling panel from NanoString Technologies. F Tumour volumes of mice used to profile the immune infiltrate by FACS analysis were measured up to Day 12 (n of 5). G Tumour weights of mice used to profile the immune infiltrate by FACS analysis at time of harvest were measured. H FACS analysis of in vivo tumour samples. Data show cell counts of CD3+, CD8+ and CD4+ cells gated from viable cells. I Cell counts of foxp3+ cells gated from viable cells. J Cell counts of PD-L1+ and PD-1+ cells gated from viable cells. For data sets (F–J), data presented are mean values ± SEM from 1 biologically independent experiment. vehicle n = 5, RT3D n = 5, talazoparib n = 5 and combination n = 5 animals per group. P values were derived where * = p value, **= p value < 0.01 and *** = p value < 0.001. Source data are provided as a source data file.
