Immune Checkpoint Modulators
One immunotherapy approach is to block the activity of certain proteins that limit the strength of immune responses. These proteins normally keep immune responses in check to prevent overly strong responses that might damage normal cells as well as abnormal cells. In cancer cells, these “checkpoint” proteins may be abnormal and may help tumors to evade the immune response.
Blocking one of these checkpoint proteins could lift the brakes on the immune system, enabling it to destroy cancer cells. The first immune checkpoint modulator to gain Food and Drug Administration (FDA) approval is called ipilimumab (Yervoy). This immunotherapy drug, a monoclonal antibody, blocks the activity of a checkpoint protein called CTLA4 and has been approved to treat advanced melanoma.
Immune Cell Therapy
An experimental form of immunotherapy is adoptive cell transfer (ACT). In one form of ACT, cytotoxic T cells that have invaded a patient’s tumor, called tumor-infiltrating lymphocytes (TILs), are harvested. The cells with the greatest antitumor activity are selected, and large populations of these cells are grown in the laboratory and activated with cytokines. The cells are then infused back into the patient.
The idea is that TILs already have the ability to target tumor cells but may not be present in sufficient amounts to exert an antitumor effect. If the activity of the TILs is being suppressed by the tumor cells, it may be possible to overcome that suppression by exposing the tumor to massive amounts of activated TILs.
In another form of ACT, often referred to as CAR therapy, a patient’s T cells are collected from their blood and genetically modified to express hybrid proteins called chimeric antigen receptors (CARs) before they are expanded and infused into the patient. The CAR allows the cells to attach to specific proteins on the surface of cancer cells, which activates the T cells to attack those cells.
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 taken from tumor cells. They are designed to treat cancers that have already developed by strengthening the body’s natural defenses against the cancer. Treatment vaccines may act in any of several ways:
- to delay or stop the growth of cancer cells
- to cause tumor shrinkage
- to prevent cancer from coming back
- to eliminate cancer cells that have not been killed by other forms of treatment
Developing effective cancer treatment vaccines requires a detailed understanding of how immune system cells and cancer cells interact. To be effective, cancer treatment vaccines must stimulate specific immune responses against the correct target. The immune responses must also be powerful enough to overcome the barriers that cancer cells use to protect themselves from attack by B cells and killer T cells.
Recent advances in understanding how cancer cells escape recognition and attack by the immune system are now giving researchers the knowledge required to design cancer treatment vaccines that can accomplish both goals.
In 2010, the FDA approved the first cancer treatment vaccine, sipuleucel-T (Provenge), for use in some men with metastatic prostate cancer.
Yet another type of immunotherapy uses immune-modifying agents, such as cytokines, antibodies, and growth factors, to enhance the body’s immune response against cancer. Cytokines are signaling proteins that are produced by white blood cells, and they help regulate immune responses. Two types of cytokines are used to treat patients with cancer: interferons and interleukins.
Immune-modifying agents may work through different mechanisms. A 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.
Research at NCI
Immunotherapy research at NCI is done across the institute and spans the continuum from basic science discoveries to clinical research applications.
The Center of Excellence in Immunology (CEI) brings together researchers from across NCI and other NIH institutes to foster the discovery, development, and delivery of immunotherapy approaches to prevent and treat cancer and cancer-associated viral diseases.