Immune checkpoint blockade with specific
antibodies can accelerate anti-
tumor immunity, resulting in clinical responses in patients with various types of
cancer. However, these
antibodies achieve only partial
tumor regression. Thus, a wide variety of treatment combinations based on
programmed death-ligand 1 (PD-L1) pathway inhibition are under development to enhance such
therapeutic effects. In this study, the effects of combination treatment using
PRI-724, a selective inhibitor of CBP/β-
catenin, and an anti-PD-L1 antibody were examined in a mouse model of
colon cancer liver
metastasis. Mice were inoculated with SL4
colon cancer cells to produce metastatic liver
tumors. The combination treatment resulted in regression of
tumor growth, whereas monotherapy with each treatment individually failed to exhibit any anti-
tumor activity. In addition, co-administration of the inhibitor and antibody induced CD8+CD44lowCD62Llow cells and
interferon (IFN)-γ production in CD8+ T-cells in the liver compared with that in control mice. Administration of an anti-CD8 antibody mitigated the anti-
tumor effects of the combined treatment of
PRI-724 and anti-PD-L1 antibody. In conclusion, targeting CBP/β-
catenin, combined with PD-1/PD-L1
immune checkpoint blockade, shows potential as a new therapeutic strategy for treating liver
metastasis during
colon cancer.