Figure 7.

FOXP3 ASOs promote additive efficacy when combined with αPD-1 immune checkpoint blockade. Mice were treated with ASO 895310 (50 mg/kg BIW) and αPD-1 (10 mg/kg BIW) alone or in combination from day 1 post A20 tumor-implantation. ASO was dosed for the duration of the study. αPD-1 was dosed six times. N=12 per group. Mice were sacrificed when tumors exceeded 1500 mm³ or after 40 days. (A) Spider plots indicate tumor volumes. Survival panel shows percent surviving mice vs time. (B–G) Foxp3, CD8a/CD8b and Granzyme messenger RNA expression in tumors and spleens from terminal samples. (H) Model of ASO targeting of FOXP3 expression to reduce Treg immunosuppressive capacity and promote antitumor immunity. Data in figure represent two independent experiments. CR, complete responses. Error bars are ±SEM *, p≤0.05; **, p≤0.01; ***, p≤0.001; ****, p≤0.0001 by one-way analysis of variance with Dunnett’s post-test relative to PBS group. Survival analysis (A) was done by log-rank Mantel-Cox test. ASOs, antisense oligonucleotides; BIW, two times per week; IFN, interferon; PBS, phosphate buffered saline; PD-1, programmed cell death 1.