In the past decade, researchers have made a number of incredible strides in the fight against cancer. One of the most promising approaches to cancer treatment and cure remains immunotherapy. This approach has received a great deal of attention in recent years since former President Jimmy Carter’s miraculous turnaround after receiving immunotherapy to treat his metastatic melanoma. Immunotherapy, as the name implies, is a field of research that seeks to bolster the body’s natural immune defenses and retrain it to identify and destroy tumorous cells successfully.
Researchers have pursued more than one way of supporting a patient’s own immune system. One approach involves stimulating the immune system to either attack harder or smarter. Another primary approach involves the growth of man-made immune system proteins that are then introduced into a patient’s body.
Some immunotherapies provide only a generalized boost to the immune system, while others train the immune system to recognize certain biomarkers. Immunotherapy has also proven effective when used in concert with other treatments, so many researchers are looking into how it interacts with other established and experimental techniques.
An Overview of the Immune System
To understand how cancer immunotherapies work, it is essential to know the basic functions of the immune system. This system consists of a number of special cells and substances that protect the body from infection and kill foreign bodies when they enter the body.
To accomplish its goal, the immune system keeps track of all substances that are found in the body. When immune cells encounter something that they identify as “foreign,” they raise an alarm and launch an attack. Identifications are typically made by proteins found on cell surfaces. The immune system knows which proteins are native and considers anything that it does not recognize an invader.
When it comes to cancer cells, the immune system often fails. Cancer occurs when normal cells become altered in a specific way and then begin to replicate uncontrollably. Since these cells develop from healthy cells, the immune system does not always recognize them as foreign, as would be the case with a germ or virus.
By the time that cancer cells become different enough for the body to recognize them as foreign, it is rare that the immune system can launch a strong enough attack to obliterate the tumor. Also, cancers themselves can trick the immune system by bypassing the body’s checkpoint system. For this reason, much of immunotherapy is aimed at helping the immune system identify cancer cells more effectively and then create a stronger response to destroy tumors.
Common Types of Cancer Immunotherapy
Several different types of cancer immunotherapy are currently in clinical phases, and only a handful have been approved for use in cancer patients. Some of the common types include:
- Immune checkpoint inhibitors
The immune system has natural “checkpoints” that help avoid an autoimmune attack, which is when the immune system targets healthy cells. These checkpoints disable the immune system so that it does not do damage to normal cells. Cancer cells take advantage of these checkpoints by using them to trick the immune system into thinking they are healthy cells.
Immune checkpoint inhibitors are designed to take the brakes off the immune system so that they can get past these checkpoints and recognize cancer cells as disease. However, taking the brakes off of the immune system also increase the risk of an autoimmune response.
Several checkpoint inhibitors have gained approval from the FDA for use in patients, including ipilimumab, which helps treat advanced melanoma. This specific drug blocks the activity of a checkpoint protein called CTLA4. This protein inactivates T-cells that have a cytotoxic effect.
- Monoclonal antibodies
Researchers can synthesize immune system proteins in the lab and then train them to recognize specific biomarkers found only on cancer cells. Once the proteins show appropriate specificity in attacking the cancer cells, they are proliferated and then introduced directly into the patient’s body, where they attack the cancer. Because of the normal mechanisms of the immune system, these synthetic cells “teach” other cells in the body to also attack the tumor.
A specific subclass of therapeutics antibodies called antibody-drug conjugates (ADCs) has proven especially beneficial to patients with cancer. ADCs chemically link antibodies to a toxic substance. The antibody binds to a target molecule expressed on the surface of a cancer cell.
Then, the toxic substance, whether a poison, a drug, or a radioactive compound, is taken up by the cancer cell. Some of the ADCs approved for use among patients are brentuximab vedotin for Hodgkin lymphoma and non-Hodgkin T-cell lymphoma and ado-trastuzumab emtansine for breast cancer.
- Cancer vaccines
All vaccines are substances meant to trigger an immune response against a certain disease. Typically, vaccines are given to healthy people to prevent a future infection. However, vaccines can also be used to prevent or treat cancer. Some vaccines are used to prevent diseases that are precursors to cancer, such as human papilloma virus (HPV), which can lead to cervical cancer. To treat cancer, vaccines are usually created using the patient’s own cells.
The FDA approved the first therapeutic cancer vaccine in 2010, which is called sipuleucel-T. The treatment involves removing immune cells, training them to recognize cancer cells involved with metastatic prostate cancer, and then reintroducing them to the body. Vaccines are now being produced to treat lung, brain, and breast cancer.