The Immuno-Oncology Revolution
For decades, it has been known that certain immune cells called cytotoxic T lymphocytes (CTLs) can destroy cancer cells, yet they fail to play this key role in many patients suffering from cancer. Today, we know that tumors produce “immune checkpoint proteins” that suppress the activity of CTLs, effectively putting “the brakes” on the immune system’s ability to fight cancer. This discovery of immune checkpoints spurred the immuno-oncology revolution and led to the development of a new class of anti-cancer therapeutics, called “checkpoint inhibitors.”
Why Do So Few Patients Respond To Checkpoint Inhibitors?
Despite the promise of checkpoint inhibition, not all patients with cancer benefit from this type of treatment. Too often, checkpoint inhibitor therapy “releases the brakes” on the immune system, but fails to mount an effective attack against the tumor, which continues to grow. When this happens, treatment with a checkpoint inhibitor may have limited clinical benefit.
How Can We Improve Patient Response To Checkpoint Inhibitors?
It is believed that the activity of checkpoint inhibitors may be dramatically increased by combining these anti-cancer therapeutics with an immune activator to stimulate T cell activity. Many different immune activators have been investigated and the Toll-like receptor 9 (TLR9) agonist CpG oligonucleotide (ODN) has been found to be the strongest at stimulating anti-tumor effects. Checkmate Pharmaceuticals believes that this combination of two important cancer-fighting mechanisms: CpG-A ODN to stimulate a T cell response to attack the tumor, along with checkpoint inhibition to release the tumor’s suppression of the immune system, may result in increased clinical benefits for patients.