Unleashing the Immune System to Attack Cancer
Immunotherapy is a treatment that uses the body's own natural defenses to fight cancer. White blood cells (T cells) that make up the immune system can be stimulated in several ways by specially designed drugs that allow them to recognize and kill cancer cells.
Early immunotherapy drugs worked in a general way by boosting the body’s immune system to fight cancer cells. However, recent research has discovered several proteins on the surface of T cells that act like a brake, or checkpoint, preventing them from attacking cancer cells.
CTLA-4 is one such checkpoint. Research on CTLA-4 led scientist Jim Allison in 1996 to propose blocking the protein as a cancer therapy. The findings by Allison, now chair of immunology at MD Anderson, led to the development and approval of ipilimumab, an immune checkpoint inhibitor that turns off CTLA-4 and allows the T cells to do their work. Ipilimumab has extended survival in patients with advanced melanoma.
Another checkpoint is PD-1, discovered in 2000. Several drugs have been developed to turn off PD-1 in many types of cancer, allowing existing T cells near the tumor to attack. Researchers continue to identify more checkpoints that can be exploited to fight cancer.
Adoptive cell therapy (ACT) approaches work in two ways. One method takes a patient’s own immune cells that recognize and attack cancer but are too few to succeed, multiplies their number to billions of cells in the lab, and then gives them back to patients. Another method genetically engineers a patient’s immune cells in the lab to recognize and attack their own specific cancer, expands their number and reinfuses them in the patient. Both methods are being developed in clinical trials for solid tumors and blood cancers.
Other immunotherapies fall into two general categories.
Targeted immunotherapies attack specific proteins on the surface of cells that help identify cancer and stimulate an immune response. Common types include:
Monoclonal antibodies are designed to identify specific abnormalities on the surface of cancer cells. Monoclonal antibodies attach themselves to these abnormalities, marking them as a target for the immune system.
Cancer vaccines help the body recognize cancer cells and stimulate the immune system to destroy them. Some vaccines contain cancer cells harvested from the patient’s tumor. Others contain proteins designed to attach themselves to cancer cells.
General immunotherapies are non-specific treatments that do not affect the cancer itself. They work on proteins called cytokines that send signals to stimulate the body’s immune system to fight cancer cells. Common types include:
Interleukins control the growth and activity of T cells. More than a dozen interleukins have been identified. Interleukin-2 (IL-2) is used to treat kidney cancers and melanomas that have spread to other regions of the body. Other interleukins are being studied as possible treatments for other types of cancer.
Interferons are a group of three proteins released by T cells in reaction to invading organisms. Interferons increase the immune system's reaction to cancer cells. Interferon alpha (IFN-alfa) is currently being used to treat melanoma, kidney cancer and certain types of leukemia and lymphoma.
Colony Stimulating Factors (CSF) strengthen the immune system by stimulating the production of white blood cells in the bone marrow. CSF therapies are used to help elevate low white blood cell counts after chemotherapy.
MD Anderson patients have access to clinical trials offering promising new treatments that cannot be found anywhere else.
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You’ve probably heard of immunotherapy. But what exactly is it? And who should consider immunotherapy?
At its most basic, immunotherapy uses the body’s own natural defense system to attack diseases like cancer.
Let’s start with the basics. What is immunotherapy?
Immunotherapy is a treatment that targets the body’s immune system to recognize and eradicate cancer.
How does it work?
When people talk about immunotherapy right now, they’re usually talking about immune checkpoint therapy. Immune checkpoint therapy comes from Jim Allison’s work with T cells. T cells are the soldiers of the immune system, the heavy lifters who do all the hard work. It takes two proteins working together to act as a signal that turns them on. But T cells are very well-regulated and they have off signals as well. After a short period of time, the signals on T cells cause them to turn off, which is normally a good thing, since it prevents the T cells from causing damage to the body.
The problem with cancer is that by the time it gets big enough for the immune system to detect, it’s also too large for the T cells to eradicate in a short period of time. The T cells can attack the cancer cells, but then the T cells turn off and don’t get a chance to finish the job. So if we block the “off” switch of T cells, they can continue to work and destroy the tumors.
What are the benefits of immunotherapy compared to more conventional treatments, such as chemotherapy and radiation?
Traditional therapy targets tumor cells, but immunotherapy targets T cells. And whereas conventional therapy treats a specific type of cancer, with immunotherapy, you can treat multiple tumor types.
Another benefit is that the immune system is always evolving and learning. It’s a living system in our bodies. So just because treatment ends, that doesn’t mean the benefits stop. Once it learns to recognize cancer in your body, the immune system will continue to target those cells if it sees them again.
Which diseases is immunotherapy working best on?
So far, immunotherapy has proven most effective in treating melanoma, non-small cell lung cancer, bladder cancer, kidney cancer, stomach cancer, liver cancer, head and neck cancers, and lymphoma. All of those have FDA-approved immunotherapy drugs available to treat them.
What diseases is immunotherapy showing promise for?
Who should consider participating in immunotherapy clinical trials?
Any cancer patient, regardless of their stage of disease, should consider enrolling in a clinical trial involving immunotherapy. We have immunotherapy clinical trials for many cancer types for patients in the early stages of cancer, for those whose cancer has metastasized, for those who have tried everything else and for those who haven’t tried anything at all yet.
These days, everyone is talking about precision medicine. Well, you don’t get much more personalized than your own immune system. The most important thing is for patients to have a conversation with their physicians to discuss their options. Their doctors are in the best position to help them navigate all the clinical trials available.
What’s new in immunotherapy research?
We still don’t understand why some patients get great responses and some don’t. So we’re going back to basic lab research. That’s what Jim Allison’s work was. He is a general researcher doing lab work. But he tried his finding first in mice, and then in patients.
It’s kind of cyclical. We take what’s been learned in lab to clinical trials, and then take the results of clinical trials back to the lab. This way, we can understand the mechanisms of resistance and develop new strategies.
Where do you see immunotherapy in 10 years?
I think it’ll be the backbone of a lot of our cancer treatments, whether used alone or in combination with more conventional treatments, such as chemo, radiation and even targeted therapy. Also, I see it being used to treat many cancer types, not just melanoma.
What advice would you offer to a patient who is considering an immunotherapy trial?
Speak with your doctor to weigh the risk/benefit ratio and to understand the toxicity and side effects, because they can be very different from those associated with more traditional therapies.
Anything else you want patients to know?
I want to encourage patients to let us collect blood samples and tumor tissues for research purposes. We need their participation to learn so we can understand cancer better.
Editor's note: We updated the list of diseases on which immunotherapy works best and is showing the most promise on Sept. 28, 2017, to reflect additional cancers that can now be treated with FDA-approved immunotherapy drugs since this post was originally published in June 2016.
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