Fig. 5

tbLN-directed CTLA4 blockade demonstrates dose-dependency in tumor inhibition but not in severity of irAEs. To examine the dose-dependency of CTLA4 mAb on therapeutic efficacy and toxicity, 1 mg/kg or 5 mg/kg on day 4 or cumulative dosage 10 mg/kg (5 mg/kg × 2) day 4 and 8 was administered to tbLN of unilaterally inoculated mice. A. Experiment outline B. Normalized SiLN in vivo luciferase activity of individual mice. (Control, n = 12; 1 mg/kg, n = 3; 5 mg/kg, n = 6; 10 mg/kg, n = 6) C. tumor inoculated SiLN weight normalized to mouse body weight. (Control, n = 12; 1 mg/kg, n = 3; 5 mg/kg, n = 6; 10 mg/kg, n = 6) D. ex vivo luciferase activity of the SiLN, PALN, Liver and lung as measured on day 42 post tumor inoculation. (Control, n = 12; 1 mg/kg, n = 3; 5 mg/kg, n = 6; 10 mg/kg, n = 6) E. Complete response rate (Control, n = 12; 1 mg/kg, n = 3; 5 mg/kg, n = 6; 10 mg/kg, n = 6) F. Plot showing overall survival of mice in each group. (Control, n = 20; 1 mg/kg, n = 6; 5 mg/kg, n = 8; 10 mg/kg, n = 14) G. Spleen index of each group. Spleen index was calculated by dividing the spleen weight at experimental endpoint by the mouse body weight. (No tumor control, n = 12; Control, n = 6; 1 mg/kg, n = 3; 5 mg/kg, n = 6; 10 mg/kg, n = 8) H. Severity of different irAEs (Pneumonia: No tumor control, n = 17; Control, n = 20; 1 mg/kg, n = 4; 5 mg/kg, n = 6; 10 mg/kg, n = 11; Glomerulonephritis and Vasculitis: No tumor control, n = 17; Control, n = 13; 1 mg/kg, n = 4; 5 mg/kg, n = 6; 10 mg/kg, n = 11; Sialadenitis: No tumor control, n = 17; Control, n = 13; 1 mg/kg, n = 4; 5 mg/kg, n = 2; 10 mg/kg, n = 9). Statistical analyses were done using ANOVA with Tukey’s test. *P < 0.05, **P < 0.01, and ****P < 0.0001. Data are represented as means ± SEM