What are Cancer Neoantigens? The Link Between Neoantigens and Immunotherapy

By Bishoy Faltas, M.D.

Our immune system has evolved over time to enable us to fight infections. Our bodies need to differentiate between our own cells (self) and cells from bacteria and viruses (non-self) in order to mount an effective attack to eliminate the invaders. In order to do that, our immune system has learned to recognize fragments of foreign proteins, which carry a specific sequence that marks them as “targets” for the immune system. We call these antigens.

Cancer cells thrive because they hide from the immune system, but their disguise is not perfect. Cells typically become cancerous because of changes in their genetic makeup. These same changes can result in proteins that the immune system is able to recognize as foreign. These are called neoantigens, and refer to new cancer antigens that cue the immune system to attack the cancer and eliminate it.

New sequencing technologies enable us to detect new cancer antigens unique to each patient.
The immune system just needs a little help to make this happen. To tip the balance in favor of the immune system, we now use drugs called immune checkpoint inhibitors. These unleash the power of the immune system to attack the tumor. A good way to think about it is as “releasing the brakes” off the immune response. This approach to treatment is very promising for bladder cancer, especially when other treatments have failed to stop the cancer from progressing or metastasizing to other organs.

To understand which patients are most likely to respond to these immune checkpoint inhibitors, we conducted a study examining the neoantigens in bladder cancer patients at Weill Cornell Medicine. Our analyses found many differences in the neoantigens between untreated tumors and advanced tumors that had previously been treated with chemotherapy from advanced chemotherapy-resistant bladder cancers. More details on our findings can be found here:

In the future, we are hoping to use neoantigens as biomarkers that tell us which patients are most likely to respond to specific immunotherapies. A form of precision medicine, this will help us to narrowly tailor our treatment approach to each patient.

Some of our current immunotherapy treatments for people with bladder cancers include:

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