Fig. 4.
The combination of HA PD-1 Ig and hypofractionated radiation therapy (RT) results in synergistic control of Lewis lung carcinoma in mice. (A) Treatment plan: C57BL/6 mice were injected subcutaneously with 105 Lewis lung carcinoma (3LL) cells (black arrow). Mice with a tumor volume of ~ 50 mm3 were randomized into 4 groups (IgG, HA PD-1 Ig, RT + IgG, and RT + HA PD-1 Ig) and received either a total of 60 Gy radiation, administered in 3 sequential 20 Gy fractions, or i.p. injections of 200 μg HA PD-1 Ig or isotype control (IgG) every 3 days for a total of 5 doses starting on day 6, as indicated by green arrows. The insert (red arrow) shows a footpad tumor visualized by on-board cone-beam computed tomography (CBCT). (B and C) Measurements of cumulative and individual tumor volumes. Data are representative of 3 independent experiments (n = 7–9). The horizontal dotted line indicates the treatment starting tumor volume (~ 50 mm3). (D) Tumor growth delay (TGD). (E) Percentage of treated mice in RT + IgG and RT + HA PD-1 Ig groups that developed a secondary tumor in the draining lymph node (dLN) 30 days post-treatment. Bars on graphs show mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001 (Two-way ANOVA or Student's t-test).