New targets could mean better immunotherapy for colon cancer

Immunotherapies have taken cancer treatment by storm, but so far the approved therapies haven't made much progress in colon cancer. New research has zeroed in on potential drug targets that can help the immune system attack this type of cancer. 

In addition to revealing the role gut bacteria play in colon cancer, a new study from a team at the Dresden University of Technology identified two proteins for potential immunotherapies that could make that line of treatment effective for a much larger patient pool.

Immunotherapy cancer treatments are designed to help the body’s immune system locate and target cancerous cells that can otherwise grow undetected. These treatments have made a wave in the cancer space, but have so far been very limited in which kinds of cancer they can successfully treat—and they have an overall success rate of only about 20%.

Colon cancer in particular, one of the most common types of cancer, is highly resistant to immunotherapy. The immunotherapies currently available to treat colorectal cancer, like Merck’s Keytruda and Bristol Myers Squibb’s Opdivo and Yervoy, are only effective in cases of MSI-H colorectal cancer, a type of the disease marked by tumor instability that accounts for a small percentage of patients.

The problem lies in how cancerous cells hide from the immune system. The surface of a cancerous cell has a particular signal called a checkpoint protein that stops immune cells from identifying the cancer as a threat. Immunotherapies target those specific proteins to stop them from disguising the cancer. But that same mechanism limits their use: They can only target checkpoint proteins that they’ve been designed to combat. So far, the inhibitors have all been targeting proteins that show up in a minority of cases.

The team at Dresden has now identified two proteins in a significant number of colon cancer cells, B7H4 and B7H3, and tested how inhibiting those proteins would affect cancer cells.

“The result was startling,” said the study’s author, Kenneth Peuker, Ph.D., in a press release. “Tumor tissue in which these signals were disabled showed significantly slowed growth or even shrinking. We have observed that now the immune cells could invade the cancer tissue and started to control tumor cells.”

Immunotherapy treatments targeting these proteins could prove much more effective at stopping colon cancer—and this research team isn’t the first to notice. Daiichi Sankyo and AbbVie are both working on immunotherapy treatments centered around B7H3, and Mersana Therapeutics is targeting B7H4, although all are still in the earlier stages of development.

The identification of B7H3 and B7H4 as possible drug targets to boost immunotherapies came from the discovery of a link between colon cancer and gut bacteria. One of the goals of this study was to figure out the process of how cancer cells hide themselves from the immune system. The researchers found a connection to breaking the intestinal barrier, the cells lining the digestive tract meant to help the body absorb essential nutrients while keeping harmful pathogens out.

If that cell lining is compromised near a tumor, gut bacteria can leak past the intestine into the surrounding tissue, which is ultimately what allows the cancer cells to develop the two checkpoint proteins. By treating the ruptured barrier with antibiotics, the research team found that killing the bacteria also shrank the tumors and decreased their spread to the liver.