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.

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:

• A combination study of a monoclonal antibody and radioactive molecule (177Lu-J591) for people with advanced stage, malignant bladder cancers that have not responded to standard therapy
• An antibody-drug conjugate study (IMMU-132) for adults with metastatic epithelial bladder cancer who have not responded to standard treatment
• For the first-time in bladder cancer, we’re able to offer a combination treatment of two different immunotherapies (Medi 4736 and Tremelimumab) for people with stage 4 bladder cancer. This is a multi-center, global study of antibodies that may help the immune system prevent or slow the growth of bladder cancer. This study is for adults with stage 4 bladder cancer who have not yet received chemotherapy.
• An immunotherapy clinical trial for patients with urothelial cancers that exhibit Her2 overexpression or amplification. These types of bladder cancers are genetically very closely related to breast cancers.
• A combination treatment that involves a monoclonal antibody and radiation treatment for adults with metastatic bladder cancer who have not responded to standard treatment.