ADJUVANT EFFECT OF THE TLR1/2 AGONIST DIPROVOCIM SYNERGIZES WITH CHECKPOINT-INHIBITING ANTIBODIES TO ELIMINATE DISEASE

摘要

A potent human and mouse Toll-like receptor (TLR)1/TLR2 agonist was identified and optimized, Diprovocim, which exhibited an EC50 of 110 pM in human THP-1 cells and 1.3 nM in primary mouse peritoneal macrophages. In mice, Diprovocim-adjuvanted ovalbumin immunization promoted antigen-specific humoral and CTL responses, and synergized with anti- PD-L1 treatment to inhibit tumor growth, generating long-term anti-tumor memory, curing or prolonging survival of mice engrafted with the murine melanoma B16-OVA. Diprovocim induced greater frequencies of tumor infiltrating leukocytes than alum, of which CD8 T cells were necessary for the antitumor effect of immunization plus anti-PD-L1 treatment.