The adjuvant effect of the TLR1 / 2 agonist diprobossim, which shows a synergistic effect with the checkpoint inhibitory antibody and eliminates the disease.

摘要

The diprobossim identified and optimized as a potent human and mouse Toll-like receptor (TLR) 1 / TLR2 agonist showed an EC50 of 110 pM in human THP-1 cells and 1.3 nM in primary mouse peritoneal macrophages. In mice, ovalbumin immunization with diprobossim as an adjuvant promotes antigen-specific human and CTL responses and, in combination with anti-PD-L1 therapy, suppresses tumor growth, producing long-term antitumor memory and mouse melanoma. Mice engrafted with B16-OVA showed a synergistic effect of healing or prolonging survival. Although CD8T cells of tumor-infiltrating leukocytes are required for the antitumor effect of the combination of immunity and anti-PD-L1 treatment, diprobossim significantly induced the frequency of tumor-infiltrating leukocytes compared to myoban. [Selection diagram] FIG. 1A