Immunotherapy

Checkpoint inhibitors

At Seattle Cancer Care Alliance (SCCA), researchers have found a way to put your immune system back in control. Checkpoint inhibitor immunotherapy has led to impressive immune responses, even with cancers that were difficult to treat until now, such as lung cancer and melanoma (skin cancer). This science fuels SCCA’s mission to provide our patients better, longer, richer lives.

With checkpoint inhibitors showing great promise for many different cancer types, SCCA continues to study what makes this therapy work best and when it is the right option for each patient. Our immunotherapy leaders have years of experience turning research into real-world therapies. Other cancer care centers just administer these drugs — SCCA’s science is the backbone behind them.

Immunotherapy A type of therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection and other diseases. A therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection and other diseases. Some immunotherapies only target certain cells of the immune system. Others affect the immune system in a general way. Types of immunotherapy include cytokines, vaccines, bacillus Calmette-Guerin (BCG) and some monoclonal antibodies. Melanoma Cancer that begins in the melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but it can also begin in other pigmented tissues, such as the eye or the intestines.

What are checkpoint inhibitors?

Your immune system has built-in checkpoints that help it find invaders to attack, like bacteria or tumors. Cancer cells can trick these checkpoints by sending false signals. This disguises the tumors so that they appear harmless, which puts the brakes on T cells — your immune system’s anti-infection troops — and keeps them from attacking tumors.

Antibodies are Y-shaped proteins that the immune system uses to identify and fight antigens (foreign objects like viruses and tumors). Immune checkpoint inhibitors are designed to release these brakes. They block cancer’s false signals, restarting the immune system’s engines so it can attack cancer.

Antibody A protein made by immune system cells and released into the blood. Antibodies defend the body against foreign substances, such as bacteria. T cell A type of white blood cell. T cells are part of the immune system and develop from stem cells in the bone marrow. They help protect the body from infection and may help fight cancer. A type of white blood cell. T cells are part of the immune system and develop from stem cells in the bone marrow. They help protect the body from infection and may help fight cancer. Also called T lymphocyte and thymocyte.

How it works

Checkpoint inhibitor therapy is moving at a skyrocketing pace. A growing number of clinical trials and commercially available drugs are bringing this therapy to more patients and more cancer types. They can also be combined with other treatments, like adoptive T-cell therapy, to work even better together.

“I feel incredibly lucky to have been treated at an organization committed to moving the needle in research. Because of clinical trials at SCCA, we are getting to a point where they are yielding amazing results for patients like me.”
— David Dunnington, Melanoma patient

Immune checkpoint therapy is a type of antibody-based immunotherapy. You can find out about other antibody therapies at SCCA.

Antibody A protein made by immune system cells and released into the blood. Antibodies defend the body against foreign substances, such as bacteria. Antibody therapy A treatment that uses antibodies to help the body fight cancer, infection or other diseases. Monoclonal antibodies are a type of antibody made in the laboratory that can be used in diagnosis or treatment. A treatment that uses antibodies to help the body fight cancer, infection or other diseases. Antibodies are proteins made by the immune system that bind to specific markers on cells or tissues. Monoclonal antibodies are a type of antibody made in the laboratory that can be used in diagnosis or treatment. In cancer treatment, monoclonal antibodies may kill cancer cells directly; they may block development of tumor blood vessels; or they may help the immune system kill cancer cells. Immunotherapy A type of therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection and other diseases. A therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection and other diseases. Some immunotherapies only target certain cells of the immune system. Others affect the immune system in a general way. Types of immunotherapy include cytokines, vaccines, bacillus Calmette-Guerin (BCG) and some monoclonal antibodies.
Antibody therapies and checkpoint inhibitors

Unfortunately, few of the body’s 100 million naturally occurring antibodies are able to recognize cancer cells. To overcome this problem, researchers have developed ways of finding antibodies that have a specific receptor needed to work against different cancers. These are called “monoclonal antibodies” because they are of a single type that is grown in large quantities for cancer therapy.

Some antibodies target cancer directly to kill tumor cells. This approach works best against blood cancers, where rituximab (Rituxan®) is probably the most widely used antibody therapy. Rituxan kills B-cell-derived cancers such as non-Hodgkin’s lymphoma or chronic lymphocytic leukemia.

Radioimmunotherapy is a technique developed at Seattle Cancer Care Alliance (SCCA) over the last 20 years to help blood cancer patients who don’t respond to chemotherapy or who, more recently, may have stopped getting benefit from Rituxan. In the 1990s, Oliver W. Press, MD, PhD, and Frederick R. Appelbaum, MD, among others, pioneered the idea of using antibodies as biological vehicles to target radiation directly to cancer cells and thereby limit the amount of radiation that goes to healthy organs. Their work led to the subsequent development of two FDA-approved radioimmunotherapy drugs, Zevalin and Bexxar.

What Kind of Cancers can be Treated with Antibody Therapy?

While the use of radioimmunotherapy is presently confined to blood cancers, researchers have found that monoclonal antibodies selected to block key growth signals for cancer cells can be effective against solid tumors. Well-known monoclonal antibody drugs in this category include trastuzumab (Herceptin®), used to treat breast cancer, and bevacizumab (Avastin®), which is used to treat colorectal, lung, brain, kidney, and ovarian cancers.

Checkpoint Inhibitors Block Antibodies that Hide Cancer Cells from the Immune System

More recently, monoclonal antibodies have been developed that manipulate anti-tumor T-cell responses by blocking negative regulatory proteins on T-cells. These monoclonal antibodies are called immune checkpoint inhibitors. SCCA was one of the first institutions in the world to research checkpoint inhibitor immunotherapy in patients. Dr. Shailender Bhatia and Dr. John Thompson were instrumental in the clinical trials of two checkpoint inhibitors, anti-PD-1 and anti-PD-L1, to treat melanoma. This research helped to develop two recent FDA-approved checkpoint inhibitor drugs — pembrolizumab (Keytruda®) and nivolumab (Opdivo®) — that are now used to treat melanoma, lung cancer, head and neck cancers and other cancers.

Finally, monoclonal antibodies can be modified to carry a toxic substance directly to targeted tumor cells. These are called antibody-drug conjugates (ADCs). The conjugates are the attached poisons, which can be a chemotherapy drug or cell toxin. In this manner, drugs that might be toxic to normal cells can be delivered only to tumor cells without the side effects that would be caused by the drug alone. Several experimental antibody-drug conjugates are currently under study in ongoing clinical trials that are part of the SCCA Phase I clinical trials program.

View Phase I Clinical Trials

Antibody A protein made by immune system cells and released into the blood. Antibodies defend the body against foreign substances, such as bacteria. Antibody A protein made by immune system cells and released into the blood. Antibodies defend the body against foreign substances, such as bacteria. Chemotherapy Treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It may be given alone or with other treatments. Treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemotherapy may be given by mouth, injection, infusion or on the skin, depending on the type and stage of the cancer being treated. It may be given alone or with other treatments, such as surgery, radiation therapy or biologic therapy. Immunotherapy A type of therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection and other diseases. A therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection and other diseases. Some immunotherapies only target certain cells of the immune system. Others affect the immune system in a general way. Types of immunotherapy include cytokines, vaccines, bacillus Calmette-Guerin (BCG) and some monoclonal antibodies. Lymphoma Cancer that begins in the cells of the immune system. There are two basic categories of lymphomas: Hodgkin lymphoma and non-Hodgkin lymphomas. Cancer that begins in cells of the immune system. There are two basic categories of lymphomas. One is Hodgkin lymphoma, which is marked by the presence of a type of cell called the Reed-Sternberg cell. The other category is non-Hodgkin lymphomas, which includes a large, diverse group of cancers of immune system cells. Non-Hodgkin lymphomas can be further divided into cancers that have an indolent (slow-growing) course and those that have an aggressive (fast-growing) course. These subtypes behave and respond to treatment differently. Both Hodgkin and non-Hodgkin lymphomas can occur in children and adults, and prognosis and treatment depend on the stage and the type of cancer. Melanoma Cancer that begins in the melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but it can also begin in other pigmented tissues, such as the eye or the intestines. Side effects A problem that occurs when treatment affects healthy tissues or organs. Some side effects of cancer treatment are nausea, vomiting, fatigue, pain, decreased blood cell counts, hair loss and mouth sores.
Antibody therapies and checkpoint inhibitors

Antibodies selectively target a particular molecule, either on the tumor itself or another strategic location.

Champions

SCCA was one of the first institutions in the world to research checkpoint inhibitor immunotherapy in patients. Dr. Shailender Bhatia and Dr. John Thompson were instrumental in the clinical trials of two checkpoint inhibitors, anti-PD-1 and anti-PD-L1, to treat melanoma. This research helped to develop two recent FDA-approved checkpoint inhibitor drugs — pembrolizumab (Keytruda®) and nivolumab (Opdivo®) — that are now used to treat melanoma, lung cancer, head and neck cancers and other cancers.

In fact, President Jimmy Carter received FDA-approved checkpoint inhibitor immunotherapy for Stage IV metastatic melanoma that was based on clinical trials research at SCCA. The extraordinary science that helped cure him has provided real hope for patients worldwide.

Immunotherapy A type of therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection and other diseases. A therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection and other diseases. Some immunotherapies only target certain cells of the immune system. Others affect the immune system in a general way. Types of immunotherapy include cytokines, vaccines, bacillus Calmette-Guerin (BCG) and some monoclonal antibodies. Melanoma Cancer that begins in the melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but it can also begin in other pigmented tissues, such as the eye or the intestines. Metastatic A metastatic cancer is a cancer that has spread to other areas of the body by way of the lymph system or bloodstream. Stage The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer and whether the cancer has spread from the original site to other parts of the body.
“Seattle Cancer Care Alliance continues to be at the forefront of groundbreaking clinical trials for checkpoint inhibitors. That’s because our team has long held a strong belief that the immune system has the power to eradicate cancer cells completely.”
— Shailender Bhatia, MD, Medical Oncologist