Extended Data Fig. 10: Efficacy of ICT in combination with targeted therapy directed against Cxcr1/2 and treatment effects on immune microenvironment.
A. Tumor volume of mice bearing established orthotopic iKRAS tumors (tumor volume ~250mm3 prior to treatment initiation) treated with control or anti-LAG3 + anti-41BB antibodies or combination (anti-LAG3 + anti-41BB + SX-682) for 4 weeks (n = 10 mice/group). Two-sided Student’s t-test. B. Tumor volume of mice bearing established orthotopic iKRAS tumors (tumor volume ~250mm3 prior to treatment initiation) treated with control or anti-PD1 + anti-CTLA4 antibodies or SX-682 or anti-PD1 + anti-CTLA4 + SX-682 for 4 weeks (n = 10 mice/group). Two-sided Student’s t-test. C. Body weight of mice (top left), before (pre-treatment), during (2 weeks) and after (4 weeks) treatment with control, SX-682 or combination (anti-LAG3 + anti-41BB + SX-682) for 4 weeks (n = 4 biological replicates). Mouse toxicity tests including creatinine, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin and alkaline phosphatase in the indicated treatment groups (n = 4 biological replicates). Representative images of H&E staining (middle) of the lung, heart, liver, kidney and spleen in the indicated treatment groups (n = 4 mice/group). Inset (bottom) shows representative H&E staining of liver tissues in the indicated treatment groups at higher magnification. D. CyTOF analysis of tumors from syngeneic iKRAS 2 and iKRAS 3 tumor bearing mice with equivalent tumor volume (~1000mm3) (n = 10 tumors/group). E. Quantification of tumor infiltrating CD45+ cells in syngeneic iKRAS 2 and iKRAS 3 tumors with equivalent tumor volume (~1000mm3) assessed by CyTOF (n = 10 tumors/group). F. Overall survival of mice bearing established orthotopic iKRAS 2 and iKRAS 3 tumors (tumor volume ~250mm3 prior to treatment initiation) treated with control or anti-LAG3 + anti-41BB + SX-682 for 4 weeks (n = 10 mice/group). Statistical differences were identified by Kaplan-Meier with log-rank test. G. Treatment schedule and monitoring procedures for preclinical trial to evaluate overall survival of mice bearing established autochthonous iKRAS tumors (tumor volume ~250mm3 prior to treatment initiation) treated with control or anti-PD1 + anti-CTLA4 antibodies or anti-LAG3 + anti-41BB antibodies or SX-682 or combination (anti-LAG3 + anti-41BB + SX-682) (n = 10 mice/group). Animals in the ‘extended’ treatment group received treatment with the combination regimen for 6 months or until death. Data in E are presented as mean ± s.e.m.
