- What Is Immunotherapy?
- Types of Immunotherapy
- Eligibility & Side Effects
- Immunotherapy By Cancer Type
What Is Immunotherapy?
Immunotherapy is one of the most exciting areas of new discoveries and treatments for many different kinds of cancer. Understanding how the immune system works is opening the doors to developing new treatments that are changing the way we think about and treat cancer.
Most people receiving immunotherapy are treated in specialized cancer centers and many of them are enrolled in clinical trials. This may change as more trials are completed and more drugs are approved by the Food and Drug Administration (FDA) to treat different kinds of cancer.
Your Immune System and Cancer
Your immune system is a network of cells, tissues and organs that works together to recognize and destroy foreign invaders such as bacteria and viruses or abnormal or unhealthy cells in your body
The most important function of the immune system is to know the difference between self and non-self. Self means your own body tissues. Non-self means any abnormal cell or foreign invader, such as bacteria, viruses, parasites and fungus. Normally, your immune system will not attack anything that it identifies as a healthy part of self.
The problem with cancer cells is that they arise from our cells, but there are differences. As they grow and spread, cancer cells undergo a series of changes, or mutations, becoming increasingly less like normal cells.
Sometimes our immune system can detect these differences and respond. Other times, the cancer cells slip through the defenses or are actually able to inhibit the immune system.
Researchers have known for many years that our immune systems do recognize and attack cancer cells.
But, the progress being made today in immunotherapy is the result of new understanding about the complex interaction between the immune system and cancer.
The goal of the field of immuno-oncology, also known as tumor immunology, is to understand exactly how the immune system interacts with the cancer, and then use that information to develop new immunotherapy treatments.
Types of Immunotherapy
The key to successful immunotherapy is to make sure that the immune system can detect the presence of cancer cells, identify them as abnormal and mount a defense against them.
Today, there are multiple approaches to immunotherapy for cancer, but they basically fall into two broad categories:
- Agents that boost the immune response. This approach uses a drug or agent that stimulates the immune system. The idea behind this is that a generalized, “revved up” immune response will be more effective in fighting the cancer.
- Agents that enable the immune system to recognize and fight the tumor. 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.
Boosting the Immune Response
These agents have been used for years and 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.
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.
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.
This type of immunotherapy requires very special facilities and is only being done in clinical trials. Studies with certain kinds of adoptive T cell therapy have shown excellent results in children and adults with leukemia and lymphoma and more trials are underway.
Enabling the Immune Response
These 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.
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 cancertypes, 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.
Eligibility & Side Effects
There is widespread interest and excitement throughout the cancer community about the potential for using immunotherapy to treat many different kinds of cancer. As researchers learn more about the interaction between our immune system and cancer, they will be able to apply that knowledge to more and more treatment options.
Most people who receive immunotherapy today have cancers that are advanced. Their cancers have either recurred and spread after primary treatment, or were diagnosed with advanced stage cancers. At this time, most immunotherapy is still given in specialized cancer centers and mostly as part of a clinical trial.
As the field of immunotherapy moves forward, researchers will begin new clinical trials with people who are at high risk for having their cancers recur or spread.
There are some people who cannot receive immunotherapy. These individuals often have health problems that make it impossible to take these drugs safely.
If you are interested in immunotherapy, talk about your options with your doctor and treatment team.
Side Effects of Immunotherapy
Immunotherapy, regardless of the approach used, does have side effects. The side effects of immunotherapy are usually different from those experienced by people receiving chemotherapy and will be different from person to person depending on the type of treatment used.
The most common side effects of immunotherapy are:
- Flu-like symptoms
- Drops in blood pressure
- Less common side effects are:
- Colitis or other gastrointestinal problems
- Thyroid problems
- Lung problems
It is critical that anyone taking any form of immunotherapy communicate with their doctors and treatment teams and let them know immediately if they are experiencing any side effects—or unusual symptoms. The side effects of immunotherapy can be managed effectively once they are identified.
At this time, little is known about what, if any, long term effects immunotherapy might have. As more and more people with advanced disease survive for longer periods of time, this will become an important area to study and understand.
How Do I Know If It’s Working?
It is important to know that when people with cancer receive chemotherapy or radiation therapy, it is usually possible to measure the effects of the treatment within a few days or weeks. But, some immunotherapy drugs take longer to work—to stimulate the immune system.
This means that it can take longer to see the benefits of treatment when they occur. This is also called a delayed response. In some instances, the cancer can appear to get worse before it gets better. This is thought to be the result of an inflammatory reaction, not the actual growth of the cancer cells.
This wait to see if the treatment is working can be a difficult time for many people receiving these drugs. They don’t know if the response is delayed or if the therapy is not effective. Many doctors now wait longer to do scans and other tests to measure the response to immunotherapy in order to give the drugs time to work.
In many cases, the responses are partial, meaning the tumor shrinks or remains stable, but does not disappear. It is also important to remember that not everyone with cancer will respond to these therapies
There is genuine excitement about the promise of immunotherapy. For many types of cancer, even those that have traditionally been very hard to treat, the response rates to these therapies are higher than those from other types of therapy. One very encouraging factor is that many of these responses are very “durable,” or long lasting. Responses that were once measured in weeks or months are now lasting for years.