August 13, 2019
National Cancer Institute/Duncan Comprehensive Cancer Center at Baylor College of Medicine
This pseudo-colored scanning electron micrograph shows an oral squamous cancer cell (white) being attacked by two cytotoxic T cells (red), part of a natural immune response. Researchers are creating personalized cancer vaccines by loading neoantigens identified from the patient's tumor into nanoparticles.
One of the most exciting advancements in cancer treatment in recent years is immunotherapy, which uses the body's own immune system to fight cancer. Many people became aware of immunotherapy when former President Jimmy Carter announced he was successfully treated for metastatic melanoma in 2015, but cancer immunotherapy actually comprises several types of treatments.
The type of immunotherapy Carter received is called an immune checkpoint inhibitor, which essentially works by "uncloaking" cancers, such that tumor cells can be more readily recognized by the patient's own immune system. Cancers often develop sophisticated means to evade immune cells, whose functions are to detect and eliminate foreign or problematic cells throughout the body. Immune checkpoint inhibitors reverse this process by blocking proteins on a class of immune cells called "T cells" that restrict T-cell function. By blocking these proteins, the immune checkpoint inhibitors release these brakes, thus allowing the T cells to attack.
Since the U.S. Food and Drug Administration approved the first checkpoint inhibitor in 2011 to treat metastatic melanoma, six immune checkpoint inhibitors have been FDA-approved to treat a number of different cancer types, including lung, bladder, stomach, Hodgkin and non-Hodgkin lymphomas, head and neck, liver, kidney, colorectal, and triple-negative breast cancers. Clinical trials are ongoing at major cancer centers such as the Sidney Kimmel Cancer Center – Jefferson Health, and we expect additional approvals for different cancer types and stages in the future.
A second major class of immunotherapeutics used to treat cancer are called monoclonal antibodies (mAbs), which target specific proteins on the surface of tumors. Whereas immune checkpoint inhibitors unmask tumors and allow them to be detected by T cells, mAbs function through a guided missile approach, directing tailored antibodies to proteins that are preferentially present in cancer cells.
This is still an area of active research, but major successes have already been seen for using mAbs in specific cancer types. For example, a subset of breast cancer patients have benefited from treatment with trastuzumab (also known as Herceptin), a monoclonal antibody that targets the HER2 protein. This therapy is effective in patients whose tumors are reliant on HER2 to thrive.
Third, there is adoptive cell therapy, which boosts the power of the patient's own immune system by increasing the number of cancer-targeting T cells. Currently, the only FDA-approved adoptive cell therapy is chimeric antigen receptor (CAR) T-cell therapy, which modifies the patient's own T cells so that they can be used to destroy the cancer. To undergo T-cell therapy, the patient's T cells are collected at the hospital and sent to a laboratory where they are introduced to the chimerical antigen receptors (CARs), which will allow the T cells to bind to proteins on the surface of the cancer cells and eradicate the tumor.
These modified CAR T cells are returned to the hospital where the patient receives them via intravenous infusion. As such, adoptive cell therapy is a means by which a patient's own T cells are removed, get "trained" outside the body, and are reintroduced. CAR T-cell therapy is currently only approved for a subset of blood cancers, and as with all immune therapies, there are risks and potentially serious side effects when altering or enhancing an individual's immune cell function.
Tumor-infiltrating lymphocyte (TIL) therapy is another type of adoptive cell therapy. Unlike CAR T-cell therapy that uses T cells circulating in the blood, TIL therapy uses cells collected from within the tumor. These T cells, which can already recognize and kill the cancer cells, are then expanded in the laboratory and infused back into the patient. TIL therapy appears promising in preliminary studies.
As exciting as the current advances regarding immunotherapy have been, there are still significant limitations. Only a minority of patients experience remarkable responses like President Carter and immunotherapy is only approved to treat a small number of cancers. But our research continues and we are now working both in the laboratory and in clinical trials to better understand the immune system and how it interacts with cancer, to better identify which patients will respond to immunotherapy, and to determine how we can use immunotherapy to treat more patients.
Karen E. Knudsen, Ph.D.
Finally, cancer researchers are also working to develop therapeutic cancer vaccines. These are different from the vaccines that we usually think of that help prevent disease; cancer treatment vaccines are given to people who have cancer to boost the immune system so that it will attack the cancer. The vaccines may be created from a person's own tumor cells or made up of proteins (antigens) found on the surface of the tumor.
There is currently only one FDA-approved therapeutic vaccine, which is used to treat some patients with metastatic prostate cancer, but there are studies being conducted on therapeutic vaccines for various cancer types, including colorectal cancer and glioblastoma.
The entire cancer community is looking to improve upon and expand our options for currently available immunotherapies, and there are also several types of immunotherapy on the horizon that are not yet FDA-approved for patients, but are being tested in the laboratory or in early clinical trials.
If you want to learn more about immunotherapy as a potential treatment option, talk to your health care provider. They can provide you with detailed information about the different kinds of immunotherapy, potential side effects, risks and benefits associated with each treatment, any available clinical trials for which you fit the criteria, and more.
Karen E. Knudsen, Ph.D., enterprise director at the Sidney Kimmel Cancer Center – Jefferson Health, oversees cancer care and cancer research at all SKCC sites in the Greater Philadelphia region. She writes occasionally on topics related to cancer.
