Some immunotherapies work by enhancing the immune system overall, without targeting specific cancer cells. These types of immunotherapies include:
- Interleukins, which are naturally occurring proteins that help cells communicate, in order to regulate cell growth and immune response. Interleukins are a subset of cytokines, molecules which modulate how cells behave and stimulate other types of immune cells to further enhance treatment response. Interleukins made in the laboratory are used to modify biological responses to boost the immune system. More than fifteen types of interleukins have been identified, each with its own immunological function.
- Interferons, another type of cytokine, which play an important role in regulating many types of cell function. Interferons can help the immune system fight cancer by inhibiting cell division, which can slow or stop the growth of cancer.
- Colony stimulating factors that can strengthen the immune system and protect against infection by increasing the number of white blood cells produced in bone marrow.
The purpose of cancer-targeting immunotherapy is to modify the immune system to recognize that the cancer is foreign to the body and needs to be attacked. This can be difficult, because the differences between cancer cells and healthy cells are often quite small and hard to detect.
Additionally, white blood cells have “immune checkpoint” molecules that alert cells to either “engage and fight” or “ignore and rest” when it recognizes something in the body as being foreign. The checkpoint molecules prevent our immune system from attacking normal cells. Drugs called checkpoint inhibitors block these molecules, allowing the immune cells to start attacking cancer cells.
One type of immune checkpoint inhibitor works by interfering with a molecular “brake” known as PD-1 or PD-L1 that prevents the body’s immune system from attacking cancer cells. Drugs in this category currently approved by the United States Food and Drug Administration (FDA) are nivolumab (Opdivo), atezolizumab (Tecentriq), pembrolizumab (Keytruda), avelumab (Bavencio), durvalumab (Imfinzi) and cemiplimab-rwlc (Libtayo).
Another type of immune checkpoint inhibitor seeks out and locks onto CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), a protein that normally helps keep immune system cells (T-cells) in check. The drug ipilimumab (Yervoy) is thought to help the immune system destroy cancer cells by blocking the action of CTLA-4.
In addition to checkpoint inhibitors, immunotherapy approaches fall into the following main categories:
- Monoclonal antibodies are lab-generated proteins that target specific tumor antigens (substances that the immune system sees as being foreign or dangerous). Some monoclonal antibodies help the immune system recognize and destroy cancer cells. Monoclonal antibodies used in the treatment of certain cancers include rituximab (Rituxan) and trastuzumab (Herceptin).
- Bispecific antibodies are lab-generated proteins that target specific tumor antigens (as do monoclonal antibodies) but also bind proteins on the surface of immune cells (T-cells). This allows the T-cells to get close to and destroy the cancer cells. Blinatumomab (Blincyto) is an example of a bispecific antibody.
- Therapeutic vaccines can boost the immune system and have the potential to treat cancer or prevent it from recurring (coming back) after treatment. The FDA has approved vaccines for certain cancers; additionally, a number of types of vaccines are being studied in clinical trials.
- Adoptive T-cell transfer (also called cellular adoptive immunotherapy) is an approach in which T-cells are removed from the individual, grown to an increased number in a laboratory and infused back into the individual with the goal of improving the immune system’s anti-cancer response. One type of adoptive T-cell transfer is chimeric antigen receptor (CAR) T-cell therapy, which is used to treat certain blood cancers.
Immunotherapies can sometimes work well in combination with other treatment types, such as surgery, radiation, chemotherapy and targeted therapy (treatments designed to target the specific cell mechanisms that are important for the growth and survival of cancer cells).
Immunotherapies can be used as a delivery mechanism by attaching a monoclonal antibody to a chemotherapy drug to make an antibody drug conjugate (ADC). The antibody seeks out and hones in on a specific molecule on the tumor cell, bringing the chemotherapy with it. This approach can kill tumor cells or stop them from dividing while limiting the harm to normal cells. Brentuximab vedotin (Adcetris) and ado-trastuzumab emtansine (Kadcyla) are examples of ADCs.