Immunotherapy: Using the Immune System to Treat Cancer
The immune system’s natural capacity to detect and destroy abnormal cells may prevent the development of many cancers. However, cancer cells are sometimes able to avoid detection and destruction by the immune system. Cancer cells may:
- reduce the expression of tumor antigens on their surface, making it harder for the immune system to detect them
- express proteins on their surface that induce immune cell inactivation
- induce cells in the surrounding environment (microenvironment) to release substances that suppress immune responses and promote tumor cell proliferation and survival
In the past few years, the rapidly advancing field of cancer immunology has produced several new methods of treating cancer, called immunotherapies, which increase the strength of immune responses against tumors. Immunotherapies either stimulate the activities of specific components of the immune system or counteract signals produced by cancer cells that suppress immune responses.
These advances in cancer immunotherapy are the result of long-term investments in basic research on the immune system—research that continues today. Additional research is currently under way to:
- understand why immunotherapy is effective in some patients but not in others who have the same cancer
- expand the use of immunotherapy to more types of cancer
- increase the effectiveness of immunotherapy by combining it with other types of cancer treatment, such as targeted therapy, chemotherapy, and radiation therapy
Immune Checkpoint Modulators
One immunotherapy approach is to block the ability of certain proteins, called immune checkpoint proteins, to limit the strength and duration of immune responses. These proteins normally keep immune responses in check by preventing overly intense responses that might damage normal cells as well as abnormal cells. But, researchers have learned that tumors can commandeer these proteins and use them to suppress immune responses.
Blocking the activity of immune checkpoint proteins releases the “brakes” on the immune system, increasing its ability to destroy cancer cells. Several immune checkpoint inhibitors have been approved by the Food and Drug Administration (FDA).
Immune Cell Therapy
Progress is also being made with an experimental form of immunotherapy called adoptive cell transfer (ACT). In several small clinical trials testing ACT, some patients with very advanced cancer—primarily blood cancers—have had their disease completely eradicated. In some cases, these treatment responses have lasted for years.
In one form of ACT, T cells that have infiltrated a patient’s tumor, called tumor-infiltrating lymphocytes (TILs), are collected from samples of the tumor. TILs that show the greatest recognition of the patient’s tumor cells in laboratory tests are selected, and large populations of these cells are grown in the laboratory. The cells are then activated by treatment with immune system signaling proteins called cytokines and infused into the patient’s bloodstream.
The idea behind this approach is that the TILs have already shown the ability to target tumor cells, but there may not be enough of them within the tumor microenvironment to eradicate the tumor or overcome the immune suppressive signals that are being released there. Introducing massive amounts of activated TILs can help to overcome these barriers and shrink or destroy tumors.
Therapeutic antibodies are antibodies made in the laboratory that are designed to cause the destruction of cancer cells.
One class of therapeutic antibodies, called antibody–drug conjugates (ADCs), has proven to be particularly effective, with several ADCs having been approved by the FDA for the treatment of different cancers.
ADCs are created by chemically linking antibodies, or fragments of antibodies, to a toxic substance. The antibody portion of the ADC allows it to bind to a target molecule that is expressed on the surface of cancer cells. The toxic substance can be a poison, such as a bacterial toxin; a small-molecule drug; or a radioactive compound. Once an ADC binds to a cancer cell, it is taken up by the cell and the toxic substance kills the cell.
Immune System Modulators
Yet another type of immunotherapy uses proteins that normally help regulate, or modulate, immune system activity to enhance the body’s immune response against cancer. These proteins include cytokines and certain growth factors. Two types of cytokines are used to treat patients with cancer: interleukins and interferons.
Immune-modulating agents may work through different mechanisms. One type of interferon, for example, enhances a patient’s immune response to cancer cells by activating certain white blood cells, such as natural killer cells and dendritic cells. Recent advances in understanding how cytokines stimulate immune cells could enable the development of more effective immunotherapies and combinations of these agents.
CAR T-Cell Therapy: Engineering Patients’ Immune Cells to Treat Their Cancers
For years, the cornerstones of cancer treatment have been surgery, chemotherapy, and radiation therapy. Over the last decade, targeted therapies like imatinib (Gleevec®) and trastuzumab (Herceptin®)—drugs that target cancer cells by homing in on specific molecular changes seen primarily in those cells—have also emerged as standard treatments for a number of cancers.
And now, despite years of starts and stutter steps, excitement is growing for immunotherapy—therapies that harness the power of a patient’s immune system to combat their disease, or what some in the research community are calling the “fifth pillar” of cancer treatment.
One approach to immunotherapy involves engineering patients’ own immune cells to recognize and attack their tumors. And although this approach, called adoptive cell transfer (ACT), has been restricted to small clinical trials so far, treatments using these engineered immune cells have generated some remarkable responses in patients with advanced cancer.
For example, in several early-stage trials testing ACT in patients with advanced acute lymphoblastic leukemia (ALL) who had few if any remaining treatment options, many patients’ cancers have disappeared entirely. Several of these patients have remained cancer free for extended periods.
Equally promising results have been reported in several small trials involving patients with lymphoma. These are small clinical trials, their lead investigators cautioned, and much more research is needed.
A Living Drug
Adoptive cell transfer is like giving patients a living drug. That’s because ACT’s building blocks are T cells, a type of immune cell collected from the patient’s own blood. After collection, the T cells are genetically engineered to produce special receptors on their surface called chimeric antigen receptors (CARs). CARs are proteins that allow the T cells to recognize a specific protein (antigen) on tumor cells. These engineered CAR T cells are then grown in the laboratory until they number in the billions.
The expanded population of CAR T cells is then infused into the patient. After the infusion, if all goes as planned, the T cells multiply in the patient’s body and, with guidance from their engineered receptor, recognize and kill cancer cells that harbor the antigen on their surfaces.
Understanding Precision Medicine in Cancer Treatment
Precision medicine is an approach to patient care that allows doctors to select treatments that are most likely to help patients based on a genetic understanding of their disease. This may also be called personalized medicine. The idea of precision medicine is not new, but recent advances in science and technology have helped speed up the pace of this area of research.
Today, when you are diagnosed with cancer, you usually receive the same treatment as others who have same type and stage of cancer. Even so, different people may respond differently, and, until recently, doctors didn’t know why. After decades of research, scientists now understand that patients’ tumors have genetic changes that cause cancer to grow and spread. They have also learned that the changes that occur in one person’s cancer may not occur in others who have the same type of cancer. And, the same cancer-causing changes may be found in different types of cancer.
The Promise of Precision Medicine
The hope of precision medicine is that treatments will one day be tailored to the changes in each person’s cancer. Scientists see a future when patients will receive drugs that their tumors are most likely to respond to and will be spared from receiving drugs that are not likely to help. Research studies are going on now to test whether treating patients with drugs that target the cancer-causing genetic changes in their tumors, no matter where cancer develops in the body, will help them. Many of these drugs are known as targeted therapies.
Though experts believe that precision medicine can become an additional option for people with cancer, it is not likely to replace the cancer treatments we already have. Currently, if you need treatment for cancer, you may receive a combination of treatments, including surgery, chemotherapy, radiation therapy, and immunotherapy. Which treatments you receive will depend on the type of cancer, its size, and whether it has spread. With precision medicine, if your cancer has a genetic change that can be targeted with a known drug, you may also receive that drug.
There are drugs that have been proven effective against specific genetic changes in certain cancers and approved by the FDA. Many of these drugs are discussed in Targeted Cancer Therapies. Approved treatments should be available wherever you have cancer treatment.
Precision Medicine as a Treatment Option
Even though researchers are making progress every day, treatment using precision medicine is not yet part of routine care for most patients. Many new drugs used in precision medicine are being tested right now in clinical trials. Some clinical trials are accepting patients with specific types and stages of cancer. Others accept patients with a variety of cancer types and stages. To be eligible for precision medicine trials, your tumor must have a genetic change that can be targeted by a drug being tested.
Not Every Person with Cancer Will Have Their Cancer Tested for Genetic Changes
If there is a targeted drug approved for your type of cancer, you will likely be tested for a genetic change that might be driving it. For instance, people with melanoma, some leukemia’s, and breast, lung, colon, and rectal cancers usually have their cancers tested for certain genetic changes when they are diagnosed. Since additional genetic changes that can drive cancer may occur over time, you might also have your cancer tested if it comes back or gets worse.
If there is not an approved targeted drug for your type of cancer, you still may be tested for genetic changes. For instance, your cancer may be tested to see if you can join a precision medicine clinical trial.
How Genetic Changes in Your Cancer Are Identified
To figure out which genetic changes are in your cancer, you may need to have a biopsy. A biopsy is a procedure in which your doctor removes a sample of the cancer. This sample will be sent to a special lab, where a machine called a DNA sequencer looks for genetic changes that may be causing cancer to grow. The process of looking for genetic changes in cancer may be called DNA sequencing, genomic testing, molecular profiling, or tumor profiling.
Paying for Precision Medicine
If you have a type of cancer with a genetic change that can be treated with an approved drug, testing for genetic changes in your cancer is part of routine care. Therefore, your insurance company may cover the costs. To make sure, check with your insurance company to find out which costs it will cover.
If you join a precision medicine clinical trial, the cost of testing for genetic changes may be covered by the organization sponsoring the trial. To be sure, check with the trial staff and make sure that you understand your consent form.
If there is not an approved targeted drug for your type of cancer and you are not in a clinical trial using precision medicine, your insurance company will probably not cover the costs of having your cancer tested for genetic changes.
Testing for genetic changes requires the use of complex technology and requires the services of people with specialized training. Therefore, this testing can be expensive.
Treatment using precision medicine can also be expensive. It takes many years, sometimes decades, of research to develop drugs that target the changes that cause cancer to develop, grow, and spread. So, by the time these drugs are available on the market, they are often very expensive.
Precision Medicine Research Moving Forward
Researchers have not yet discovered all the genetic changes that can cause cancer to develop, grow, and spread. But, they are making progress and discover new changes every day. Information from this research is being collected in databases where researchers from across the country can access the data and use them in their own studies. This sharing of data helps move the field of precision medicine forward.
Once genetic changes are discovered, another active area of research involves looking for drugs that can target these changes, then testing these drugs with people in clinical trials. Clinical trials are going on across the United States.
Researchers are also working to understand and solve the problem of drug resistance that can limit how well targeted therapies work. Many researchers believe that precision medicine is the key to unlocking these secrets.
Cancer Treatment Vaccines
The use of cancer treatment (or therapeutic) vaccines is another approach to immunotherapy. These vaccines are usually made from a patient’s own tumor cells or from substances produced by tumor cells. They are designed to treat cancers that have already developed by strengthening the body’s natural defenses against the cancer.
In 2010, the FDA approved the first cancer treatment vaccine, sipuleucel-T (Provenge®), for use in some men with metastatic prostate cancer. Other therapeutic vaccines are being tested in clinical trials to treat a range of cancers, including brain, breast, and lung cancer.