The complexity of the immune system makes it a challenging area for cancer research—but it also means there are many ways to think about how to make it work. Today, there are multiple approaches to immunotherapy for cancer, but they basically fall into two broad categories:
- Agents that boost the immune response
- Agents that enable the immune system to recognize and fight the tumor.
Boosting the Immune Response
This approach uses a drug or agent that stimulates the immune system—much in the same way that getting the flu does. The idea behind this is that a generalized, “revved up” immune response will be more effective in fighting the cancer. There are several ways to boost the immune response.
- Cytokines have been used for years. They work by stimulating the growth of T cells and activating other immune cells. Interleukins and Interferon are examples of cytokines that have shown some effectiveness in treating cancer. High dose interleukin 2 (IL2) produces excellent responses in a small percentage of people with advanced melanomas and kidney cancers.
Cytokines often have significant side effects—much like having a continuous case of the flu. Monoclonal antibodies are also used to boost the immune response.
- Therapeutic Vaccines. Cancer vaccines work to trigger an active immune response against the cancer, specifically the antigens found on the surface of tumor cells. Today, there is only one cancer vaccine approved by the FDA to treat cancer, sipuleucel-T (Provenge ®).
But, there are many clinical trials underway studying vaccines for several types of cancer. This is a very promising approach, but one that is still very early in development.
More About Vaccines
We often hear the term “vaccine” as a tool used to prevent us from getting diseases, such as measles, smallpox, or the flu. There are also vaccines that are effective in preventing certain types of cancer.
The Hepatitis B vaccine prevents the development of liver cancer in people infected with the Hepatitis B virus. Gardasil ®, which protects against the HPV virus, prevents cervical cancer in women and a form of head and neck cancer. But these vaccines do not treat the cancer itself.
Yet, today vaccines are also used to treat diseases, such as prostate cancer. These vaccines are also called “therapeutic vaccines.” Vaccines used to prevent diseases do work differently than vaccines used to treat diseases once inside the body. But, the goal is the same, which is to boost the body’s immune system to recognize and attack the disease.
Killer T Cell Attacking Cancer Cell
- Adoptive T Cell therapies use T cells collected from a person’s blood. The T cells are then re-engineered and returned to the person’s blood. The goal is to produce T cells that will attack the tumor cells, and continue to reproduce and be active for long periods of time. One example of adoptive T cell therapy is called CAR-T. The CAR stands for chimeric antigen receptors.
This type of immunotherapy requires very special facilities and is only being done in clinical trials. Studies have shown excellent results in children and adults with leukemia and lymphoma. More trials with CAR-T therapy and other adoptive T cell therapies are underway.
It is important to note, however, that not all patients benefit from this treatment and that much more research is needed to determine how and when to use these potentially powerful new tools.
Adoptive T cell therapies do have side effects. In some patients, the infusion of T cells unleashes a very strong immune response called a cytokine release syndrome. This can cause high fevers and drops in blood pressure. Most people who experience these side effects do have options to help control the symptoms, including steroids, but some people may require additional treatment.
Adoptive T cell therapies are available in select cancer centers and only on clinical trials.
Enabling the Immune Response
The newest approach to immunotherapy for cancer is based on new, emerging knowledge of the ways in which the immune system interacts with cancer cells.
- Monoclonal Antibodies are versatile tools that act in different ways to treat a wide variety of cancers. Immunotherapy is one of the promising approaches for these agents. Immunotherapy using monoclonal antibodies generally works by making the cancer cells more visible to the immune system and more vulnerable to its attack.
Monoclonal antibodies are made in the laboratory and when given to patients act like the ones that your body makes naturally. Each monoclonal antibody is manufactured to identify and attach to a specific defect in cancer cells.
There are currently over a dozen monoclonal antibodies approved to treat many types of cancer. Although there are many agents being developed and tested, right now only one monoclonal antibody that is considered a form of immunotherapy is approved by the FDA.
That is ipilumumab (Yervoy ®) for advanced melanoma. Other drugs are expected to be approved soon, as more clinical trials are completed with several kinds of cancer.
- Checkpoint Inhibitors or blockade therapy. Every time the immune system is stimulated, there are checkpoints-- complex signals that stop the immune cells from attacking and destroying normal, healthy tissue.
Cancer cells use these checkpoints to put the brakes on the immune response. New treatments called checkpoint inhibitors block the ability of cancer cells to use these checkpoints to escape from the immune system and reactivate the T cells, B cells and other cells in our bodies, which can fight the tumor.
Ipilumumab (Yervoy®) is a checkpoint inhibitor (and monoclonal antibody) that has been shown to be effective in treating advanced melanoma and kidney cancer, and is now being tested for other cancer types, including lung cancer.
PD-1 inhibitors are a new group of checkpoint inhibitors that have shown great promise in clinical trials for a wide variety of cancers, including bladder cancer, kidney cancer, breast cancer and cervical cancer. In 2014, the FDA approved PD-1 inhibitors pembrolizumab (Keytruda®) and nivolumab (Opdivo®). Both are approved to treat people with advanced melanoma who no longer respond to other treatments. In March 2015, the FDA granted nivolumab (Opdivo®) expanded approval. It is now approved for use to treat people with metastatic squamous non-small cell lung cancer who no longer respond after treatment with chemotherapy.
Dr. Langer: Cancer Is Very Crafty
Checkpoint inhibitors do have side effects. They include flu-like symptoms, drops in blood pressure, fatigue and rashes. Some patients develop more severe side effects including colitis and lung problems. For most patients, these side effects are relatively mild and can be controlled effectively.
Updated March 2015