Immunotherapy for cancer is a form of treatment that uses the body’s immune system to combat the disease. Today, immunotherapy is being applied to a wide range of cancers, often in combination with other agents, and clinical trials are exploring ways of improving and expanding its effectiveness.
A particularly promising form of immunotherapy, known as immune checkpoint inhibition, uses antibodies to block proteins on cancer cells, such as CTLA4, PD-L1, and PD-L2, that evade an immune system attack on the cells. The antibody therapies allow such an attack to proceed.
Immunotherapy has been approved for the treatment of the following cancers. Not all patients with these cancers are eligible for immunotherapy. A variety of factors — the genetic makeup of the tumor cells, how far the cancer has advanced and whether it has responded to previous treatments, for example — determines if and when it may be used as part of standard treatment.
Patients with early-stage, moderate- to high-grade (fairly fast-growing) tumors often receive a vaccine consisting of a weakened, live bacterium called bacillus Calmette-Guérin. The vaccine reduces the risk of bladder cancer recurrence by sparking an immune attack on the bacteria as well as nearby cancer cells. Several immune checkpoint inhibitors have been approved for patients with advanced bladder cancer.
Some patients with advanced triple-negative breast cancer may receive the checkpoint inhibitor atezolizumab in combination with the chemotherapy drug Abraxane.
The checkpoint inhibitor pembrolizumab has been approved for some patients with advanced cervical cancers that express the PD-L1 protein.
Checkpoint inhibitors may be used in patients with advanced colorectal cancer classified as “MSI-high,” or any cancer with MSI high. MSI-high cancers have high levels of microsatellite instability, a change or mutation in short, repeated sequences of DNA.
The checkpoint inhibitor pembrolizumab has been approved for some patients with PD-L1-positive gastroesophageal cancer (meaning their tumor cells carry the PD-L1 protein, which helps the cells avoid an immune attack) or squamous cell carcinoma of the esophagus after the exhaust prior lines of therapy. The checkpoint inhibitor pembrolizumab is used to treat subsets of patients with advanced stomach or gastroesophageal cancer that tests positive for the PD-L1 protein.
Head and neck cancer
The checkpoint inhibitors nivolumab and pembrolizumab have been approved for some patients with advanced head and neck cancer.
Immune system-stimulating substances called cytokines have been used for more than a decade to treat kidney cancer. The cytokines interleukin-2 and interferon-alpha cause kidney cancers to shrink in about 10-20% of patients, with lasting remissions in some of them.
Other immunotherapies for kidney cancer include:
- checkpoint inhibitors avelumab, nivolumab, and pembrolizumab in patients with advanced disease
- a combination of nivolumab and ipilimumab, a drug targeting the CTLA-4 checkpoint protein, for some patients with advanced kidney cancer.
Immunotherapies have become especially prominent in the treatment of leukemia and other blood-related diseases and cancers. A stem cell transplant from a compatible donor is considered a form of immunotherapy because the donated blood-making cells endow patients with a new immune system that is better able to fight the disease.
Another immune system-based strategy for ALL is known as adoptive cell therapy, which treats patients with an infusion of CAR T cells, genetically enhanced T cells that mount a powerful attack on tumor cells.
The immune-signaling protein interferon alfa-2a is approved for subsets of patients with hairy cell leukemia and Philadelphia chromosome-positive chronic myeloid leukemia. Interferon alfa-2b is approved for some patients with hairy cell leukemia and aggressive non-Hodgkin lymphoma.
Immunotherapy treatments for advanced liver cancer include the checkpoint inhibitors nivolumab and pembrolizumab.
Several checkpoint inhibitors — including atezolizumab, nivolumab, and pembrolizumab — may be used in treating patients with advanced non-small cell lung cancer.
The checkpoint inhibitors nivolumab and pembrolizumab are used in the treatment of patients with classical Hodgkin lymphoma, and interferon alfa-2b is approved for some patients with follicular lymphoma.
A CAR T-cell therapy is approved for some patients with non-Hodgkin lymphoma, and tisagenlecleucel is a CAR T cell therapy for children and young adults with acute lymphoblastic leukemia.
Metastatic melanoma is the cancer in which immune checkpoint inhibitors had their first breakthrough. Today, a range of inhibitors, including ipilimumab, nivolumab, and pembrolizumab, are used to treat subsets of patients with advanced melanoma. (Nivolumab and ipilimumab are also used together in some patients.) Cytokine therapies including aldesleukin, interferon alfa-2b, and peginterferon alfa-2b are standard therapies for subsets of patients with melanoma.
Sipuleucel-T, a therapeutic vaccine made by stimulating patients’ own immune cells to target the PAP protein on prostate cancer cells, may be used to treat some patients with advanced prostate cancer. And the checkpoint inhibitor pembrolizumab is approved for some patients with advanced prostate cancer classified as “MSI-high.”
The checkpoint inhibitors avelumab and pembrolizumab are used to treat some groups of patients with advanced Merkel cell carcinoma; and the checkpoint inhibitor cemiplimab is approved for some patients with advanced cutaneous squamous cell carcinoma.
Two drugs known as immune adjuvants — imiquimod and poly ICLC — that increase the strength of the immune response are approved for some patients with basal cell carcinoma and squamous cell carcinoma, respectively. These drugs enhance the immune system’s natural response to these cancers.
This article was originally published on April 21, 2020, by Dana-Farber Cancer Institute. It is republished with permission.