Elizabeth Wayne, PhD
Everything you need to fight cancer is inside of you. Well sort of. This is the inspirational way that I like to think of cancer immunotherapy. It’s using your own immune cells to fight cancer. We do this by trying to get immune cells to recognize cancer as a foreign pathogen, thereby triggering a full-blown immune response.
Because this is a new mode of cancer treatment, I think there is very little known about it. The way it is talked about is mysteriously magical. Therefore, I wanted to use my first Oncobites article to help demystify cancer immunotherapy. I wanted to discuss this current review article in cancer immunotherapy to introduce people to the promise, challenges, and scientific pitfalls.
Before we really start this conversation, it will help to understand your immune system and how it works to protect you. There are two broad components. Your innate immune system is what you born with. It is involved in clearing infection and removing dead cells, creating a physical barrier between foreign materials and the rest of your body (think of fluid swelling around the area of a cut or animal bite). If your innate immune system comes across something interesting, it will communicate this information with your adaptive system. We call this antigen presentation. Your adaptive immune system is the immunity that you develop throughout your life as you are exposed to new environments. It is largely composed of cells that are able to remember previous pathogenic insults and reproduce itself to systemically fight an infection. But together, both of these systems coordinate to recognize, fight, and remove any disease that attacks your body.
So you may wonder if they work so well, how come our immune system doesn’t recognize cancer? Cells that have become cancerous are our own cells, they hide in plain sight. They possess many of the receptors, the receiver molecules that our immune cells look for to recognize foreign materials in your body.
Cancer immunotherapy as a genre is the study of how we get your immune cells to recognize cancer cells and launch into an immune response to kill or neutralize them.
T cells are a fundamental component of the adaptive immune system and have a role in destroying invading pathogens as well as tumor cells. CAR (chimeric antigen receptor) T cell therapy is the foremost advanced form of cancer immunotherapy and represents a huge achievement in cell engineering. In Greek mythology, chimera refers to a bad-ass fire-breathing creature that is a fusion of segments from one or more animals. It’s a bit otherworldly, but this still applies. Chimeric antigen receptor T cells are normal T cells that have been fused with enhancing parts: specialize antigen receptors fused on its surface that specifically recognizes cancer cells and machinery that will enhance their existing killing activity. In order to produce CAR T cells, a patient’s blood cells are removed by a method called leukapheresis. Then the cells undergo the process of activation (prime the cells), transduction (to place the CAR onto the cells), and expansion (produce more cells), before infusion back into the patient for treatment.
Over a decade of research has gone into identifying surface receptors that are found on cancer cells that would enable recognition by immune cells. In clinical trials in some B cell malignancies, the percentage of complete remission ranged from 70%-94%. These have led to two FDA approved CAR T therapies on the market for B cell malignancies; KYMRIAH (Novartis) and YES-CARTA (Gilead Sciences). This is an exciting hallmark for immunotherapies.
And yet despite its successes, it has limited reach. So far it has only truly been beneficial in B cells malignancies and other blood cancers. To put this into perspective, using data from the American Cancer Society 2017 Annual Facts and Figures report, only one in five of new cancer cases are blood cancers. The two available CAR T therapies, KYMRIAH and YES-CARTA are only approved for B cell acute lymphoblastic leukemia (ALL) and R/R diffuse large B cell lymphoma respectively which only account for 5% of new cancer cases in the US. These names sound really complex so let’s break it down in the chart below.
These therapies have not yet extended to solid tumors which account for over 80% of estimated new cases and deaths. This is because T cells do not migrate there or do not survive the environment long enough to have a therapeutic effect. You can check out a previous Oncobites article for more information.
Another factor in cancer immunotherapy is the cost. KYMRIAH (Novartis) while it is extremely successful in the patients that qualify costs around $475,000. The positive side is that if your treatment is unsuccessful, then the therapy is free.
There are over a dozen new CAR T drugs making their way through clinical trials, each targeting a specialized antigen and a different form of cancer. As scientists learn more about how immune cells evolve with cancer progression, we learn how to make better therapies. We have a great deal of activity to look forward to.
- D’Aloia, M. M., Zizzari, I. G., Sacchetti, B., Pierelli, L., & Alimandi, M. (2018). CAR-T cells: the long and winding road to solid tumors. Cell Death Dis, 9(3), 282. doi: 10.1038/s41419-018-0278-6