Immune checkpoint inhibitors are drugs designed to turn the immune system into a cancer-destroying weapon. However it appears that certain tumors, such as those associated with colorectal cancers, possess immune-suppressive mechanisms that thwart such therapies. Dianqing (Dan) Wu, PhD, professor of pharmacology, and colleagues have identified what might become a more effective approach to colorectal cancer immunotherapy, described on Feb. 12 in Nature Medicine.
Normally when the immune system detects cancer, it releases cytokine IL-15, which stimulates natural killer and cytotoxic T cells to attack tumors. Wu’s team found that the protein DKK2, present in high levels in colorectal cancers, impairs the IL-15 signaling pathway, thereby weakening the tumor-destroying cells. The potential therapy is an antibody against DKK2, which would act, in Wu’s words, to “inhibit the inhibitor.” Wu’s team found that the anti-DKK2 antibody kept the immune cells active and reduced tumor numbers in mice with colorectal cancer.
Wu is working with Just China, licensor of the technology, to develop anti-DKK2 antibodies into immunotherapies against colorectal cancers and potentially certain melanomas.