Figure 4.
Anti-PD-1 and anti-TIGIT combination therapy improves long-term survival following both early and late treatment courses. A. Diagram depicting experiment set up including treatment schedules. Day 0, 130,000 GL261-luc+ cells were injected stereotactically into the right stratum of female C57 BL/6 J mice (N = 70). IVIS was used to confirm tumor presence on day 7, and the animals were randomized into 10 groups. Anti-PD-1 treatment was administered on days 10, 12, and 14 via i.p. injection at a dose of 200μg/animal. Anti-TIGIT treatment was also given via i.p. injections, 200μg/animal, every other day for a total of 5 doses starting on either day 8 (Group A), 10 (Group B), 12 (Group C), or 14 (Group D). Survival was monitored. B. Kaplan meier survival curve depicts the primary endpoint for each treatment group. Anti-PD-1 treatment alone resulted in 14.3% long-term survivors, compared to 0% in the control group (p = 0.0086). Anti-TIGIT monotherapy led to 0%, 57.1%, 14.3%, and 0% long-term survival using treatment schedules A, B, C, and D respectively (p = 0.1960, 0.0006, 0.0101, and 0.1032 respectively). All combination regimens led to significant improvements in survival compared to control, including 57.1%, 85.7%, 42.9% and 57.1% long-term survivors for Groups A-D respectively (p = 0.002, 0.0002, 0.0006, and 0.0032). Combination B was also significant compared to anti-PD-1 monotherapy (p = 0.0082), while combinations A and D also trended towards significance (p = 0.0982 and 0.0929 respectively). C. Survival curve demonstrating therapeutic effect in each of the four arms following repeat survival experiment using Group D anti-TIGIT antibody treatment course (N = 54). Anti-PD-1 monotherapy resulted in 16.7% long-term survival and a median survival of 28.5 days, compared to 0% long-term survival and 24.5 days median survival in the control group (p = 0.0175). Anti-TIGIT monotherapy was not significantly different from control, with 0% long-term survivors and 25.5 days median survival (p = 0.9062). Combination treatment conferred a median survival of 44 days, including 48.0% long-term survivors (p < 0.0001). Dual checkpoint blockade was led to a significant improvement in survival compared to both anti-PD-1 and anti-TIGIT monotherapy groups (p = 0.0366 and <0.0001 respectively).