Cancer mutations and immunotherapy

We have talked about immunotherapy previously, so we know immunotherapy uses our immune system to fight cancer. It works by helping the immune system recognise and attack cancer cells. Some types of immunotherapy are also called targeted treatments or biological therapies. However, what is the relationship between cancer mutations and immunotherapy? The number of mutations in a tumor’s genome may predict how well a patient will benefit from treatment with immune checkpoint inhibitors.

Checkpoint inhibitor drugs work by blocking protein receptors that regulate the activity of T cells and other immune system components, thus boosting these cells’ antitumor activity. Bristol-Myers Squibb’s nivolumab (Opdivo®) and Merck’s pembrolizumab (Keytruda®) have made progress in clinical trials of late, with the latter therapy receiving regulatory approval from the US Food and Drug Administration in 2018.

Variation in patients’ responses to these drugs has led researchers to search for ways to predict who will benefit from which intervention. Given the potential toxicities of immunotherapy and the highly variable response to immune checkpoint inhibitors, as well as the significant economic cost of these agents, there is an urgent need for biomarkers that can predict immunotherapy response.

An example for this hypothesis is Pembrolizumab, branded as Keytruda®, is an antibody that targets PD-1—a protein that keeps the immune system’s T cells in check, inhibiting them from attacking other cells. When PD-1 is blocked by the drug in patients with MMR-deficient tumors, the researchers demonstrated that patients’ immune systems could generate a response against their cancer. Specifically, the patients who responded to treatment exhibited an increase in T cells specific to so-called neoantigens. MMR cancers are thought to carry a high number of these neoantigens, or aberrant proteins that result from gene mutations.

As we can see, there is still a lot to understand about cancer mutations; however, Clinical Researchers are working hard to offer patients new and better treatments just like immunotherapy. Althian staff is ready and will be glad to show you some of our clinical studies we have using these therapies.