They also observed that the antibody was effective in blocking a subset of melanomas when used with other immunotherapy drugs
A Yale-led research team has developed an antibody that blocks tumours in animal models of colorectal cancer. If the findings are confirmed in clinical trials, the antibody-based treatment could become an effective weapon against colorectal cancer, and possibly other cancers, that resist current immunotherapies.
The study, ‘DKK2 imparts tumor immunity evasion through β-catenin-independent suppression of cytotoxic immune-cell activation’, published in Nature Medicine, noted that certain cancers fail to respond to existing immunotherapy drugs that are designed to unleash the body's immune system against tumours. To investigate alternative approaches to these cancers, the Yale-led team focused on a protein molecule, DKK2, an inhibitor of Wnt proteins. Wnt proteins had been previously implicated in the promotion of tumours.
To explore the molecule's role in cancer, the researchers crossbred a mouse model of colorectal cancer with mice lacking DKK2. They discovered that the offspring had fewer and smaller tumours, according to senior study author and professor of pharmacology, Dan Wu.
"We found that this Wnt inhibitor, DKK2, which was thought to inhibit tumour formation, promoted tumours through suppression of tumour immunity," said Wu. "If you inactivate, neutralise or blockade this inhibitor, it causes reduction of tumour formation through activation of the host's immune system."
Based on this finding, the researchers developed an antibody to ‘inhibit the inhibitor’ and target colorectal cancers. They also observed that the antibody was effective in blocking a subset of melanomas when used with other immunotherapy drugs.
Wu, who is a member of Yale Cancer Center, believes that the antibody has potential as a new immunotherapy inhibitor to treat these and other cancers.