Checkpoint Inhibitors

The immune system needs to be able to tell the difference between normal and foreign cells, and know which to attack. To do this, checkpoints—certain proteins on the surface of T-cells (subtype of white blood cells)—activate or inactivate these T-cells to start an immune response. Checkpoint inhibitor treatments disrupt “inactivate” signals from the proteins, exposing the cancer cells as invaders and allowing the T-cells to attack.

Checkpoint inhibitors are the most widely used form of immunotherapy for cancer. Currently, four checkpoint inhibitors, given intravenously, have been approved by the Food and Drug Administration (FDA) and are on the market. These checkpoint inhibitors are:

  • Ipilimumab – treats certain types of melanoma
  • Nivolumab – treats certain types of melanoma, lung cancer, kidney cancer, bladder cancer, Hodgkin Lymphoma, and head and neck cancers
  • Pembrolizumab – treats certain types of melanoma, lung cancer, and head and neck cancer
  • Atezolizumab – treats certain types of lung and bladder cancers

The success rate of checkpoint inhibitors varies. Generally, 20 to 30 percent of patients are helped by this form of cancer therapy. Some patients with advanced disease have experienced remissions lasting for years.

The Cancer Immunotherapy Program at Intermountain Cancer Centers offers clinical trials that combine checkpoint inhibitors with other treatments to examine the effectiveness of these approaches.

Side effects of this treatment are minimal for many patients. Checkpoint inhibitors can create autoimmune issues, meaning the immune system attacks healthy tissue along with the cancer. These side effects can vary; however, most side effects can be well managed with steroid medications.

Cancer Treatment Vaccines

While some vaccines can prevent infections that may lead to cancer, cancer treatment vaccines are aimed at treating the disease once the person has it. Because cancer cells develop from a person’s own healthy cells, the cancer cells may not appear as harmful to the immune system, which may then ignore the cells instead of finding and destroying them. As such, some cancer treatment vaccines work by prompting the immune system to attack the cancer by presenting it with some piece of the cancer. These vaccines are harvested from the individual patient’s tumor and are killed, altered, multiplied, and injected back into the patient to activate the immune response.

Other cancer treatment vaccines contain antigens or proteins designed to attach themselves to cancer cells to signal an immune system response. Vaccines that are vector-based, meaning the antigens are delivered with certain weakened or killed viruses, bacteria, or yeast cells, may further stimulate an immune response.

Patients who have more advanced tumors or weakened immune systems may not be able to produce a strong immune response after vaccination. This could limit the immune system’s ability to respond to a vaccine. For this reason, some researchers think cancer treatment vaccines may work better for smaller tumors, early-stage cancers, or in combination with other treatments such as checkpoint inhibitors.

Oncolytic Viruses

The Food and Drug Administration (FDA) approved the first oncolytic virus therapy in 2015, which uses a genetically modified form of the herpes simplex virus type-1 (cold sores) so that it can’t replicate in healthy cells, that is injected into melanoma lesions. Inside these tumors, the virus replicates and causes the cells to rupture and die.

Side effects from oncolytic viruses tend to be milder than those from chemotherapy or other therapies, and can include fever, chills, fatigue, back and joint pain, nausea, and headache.

Intermountain Healthcare oncologists can determine if you would benefit from oncolytic virus therapy and administer this agent. In addition, ongoing clinical trials will determine if there will be an expanded role for oncolytic viruses.

Cell Therapy

Another form of cancer immunotherapy, called cell therapy or adoptive cell transfer (ACT), involves removing immune cells from the patient, altering them genetically to help them fight cancer, multiplying them in the laboratory and then infusing them back into the patient. This type of treatment is manufactured individually for each patient and is still experimental.

One method of cell therapy involves collecting a sample of T-cells that have permeated a patient’s tumor, called tumor-infiltrating lymphocytes (TILs). These cells are utilized because they have shown the ability to target tumor cells, but there may not be enough of them to destroy the tumor or overpower the immune suppressive signals. So, in the laboratory, TIL counts are increased and the cells are activated by treatment with immune system signaling proteins called cytokines. TILs are then infused back into the patient’s bloodstream.

Another method of cell therapy that is being actively studied is chimeric antigen receptor (CAR) T-cell therapy. This approach involves collecting a patient’s T-cells and genetically modifying them to express a protein, CAR. The population of these modified cells is grown in the laboratory and infused back into the patient. These receptors allow the modified T-cells to attach to specific proteins on the surface of cancer cells and therefore to attack the cancer cells.

Other Therapeutic Antibodies

Bispecific monoclonal antibody (BsMAb) derivatives are an alternative to cell therapy that do not require individualizing treatment for each patient. In this form of treatment, the antibodies attach to both the cancer cell and a T-cell, binding the molecular targets to simultaneously address different antigens and kill the cancer cell.

One class of therapeutic antibodies involves chemically linking antibodies to a toxic substance (e.g. a poison, a small-molecule drug, or a radioactive compound), then using the antibody portion to bind to a target molecule on the surface of the cancer cells. Once the antibody is bound to a cancer cell, the antibody is taken up by the cancer cell, which is killed by the toxic substance.

If side effects do occur in therapeutic antibody treatment, they most often happen while the drug is first delivered. Possible side effects can include fever, chills, weakness, headache, nausea, vomiting, diarrhea, low blood pressure, and rashes.