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Pancreatic cancer immunotherapy

This page was reviewed under our medical and editorial policy by

Maurie Markman, MD, President, Medicine & Science at CTCA.

This page was updated on June 20, 2022.

Immunotherapy uses drugs to help the body’s immune system attack cancer cells. Among the immunotherapy drugs used as treatment options for pancreatic cancer are drugs called checkpoint inhibitors. They are the most studied and commonly used immunotherapy drugs today.

Immune checkpoint inhibitors in pancreatic cancer

Cells in the immune system contain proteins that are referred to as checkpoints—they signal whether or not to trigger an immune response. The body uses these checkpoints to keep immune cells from attacking healthy tissue. Some cancer cells shelter themselves by co-opting these checkpoints to prevent an immune response. Immune checkpoint inhibitors block these checkpoints on cancer cells, allowing the body to recognize cancer as a threat and trigger immune response.

Checkpoint inhibitors belong to a class of drugs called monoclonal antibodies. Antibodies are proteins made by the body to seek out and attach to other proteins called antigens on a cell’s surface. Monoclonal antibodies, on the other hand, are made in a lab to mimic the role in seeking out specific antigens. If they don’t recognize a cell’s antigens, the antibodies may signal the immune system to attack that cell. Monoclonal antibodies are specifically designed to latch onto antigens common in cancer cells. They’re often given intravenously in an infusion.

A group of checkpoint inhibitors has been developed to target PD-1, a checkpoint found on immune cells, are a type of white blood cell or lymphocyte. By blocking this checkpoint, the body increases its immune reaction to cancer. These drugs include:

  • Keytruda® (pembrolizumab)
  • Opdivo® (nivolumab)
  • Libtayo® (cemiplimab)

Who may be a candidate for this type of pancreatic cancer immunotherapy?

Patients may be eligible for treatment with a checkpoint inhibitor for pancreatic cancer if their cancer:

  • Shows certain genetic changes, including those affecting mismatch repair (MMR) genes or increased levels of microsatellite instability (MSI-H), both of which are associated with Lynch syndrome
  • Has returned after treatment
  • Is inoperable or has spread to other parts of the body

Side effects of checkpoint inhibitors

Drugs such as Keytruda for pancreatic cancer frequently cause some side effects—some mild, and others more serious.

Less serious side effects of checkpoint inhibitors may include:

  • Digestive issues, such as low appetite, nausea, constipation and diarrhea
  • Fatigue
  • Pain in the muscles and joints
  • Rash

More serious side effects may include (and should be brought to the care team’s attention right away):

  • A reaction similar to an allergic reaction while receiving the infusion, including a fever, trouble breathing or dizziness
  • An autoimmune reaction, meaning the immune system starts attacking healthy tissue.

Limitations of checkpoint inhibitors

Checkpoint inhibitors typically work better on cancer that has microsatellite instability or a lack of functional mismatch repair genes in the tumor cells. However, pancreatic cancer tumors usually contain few mutations that this type of treatment typically targets, and they typically have several characteristics that protect them from immune system attacks.

Other advances in pancreatic cancer immunotherapy

Researchers are testing the efficacy and safety of PD-1 inhibitors and other checkpoint inhibitors, including ipilimumab, which is designed to affect another checkpoint and is approved to treat a few other types of cancer. Researchers are also studying other forms of immunotherapy, including dendritic cell and CAR T-cell therapies, but these have not yet been approved to treat pancreatic cancer.

CAR T-cell therapy for pancreatic cancer

CAR T-cell therapy re-engineers the body’s to add receptors that latch onto cancer cells’ antigens and destroy the cells. CAR stands for chimeric antigen receptors, which are substances created to bind to the tumor antigens. CAR T-cell therapy removes from the blood and changes them in the lab by inserting genetic information that tells them to make the receptors for specific types of cancer cells. The re-engineered are then infused back into the body.

Researchers are looking for more ways to stop pancreatic tumors from suppressing the body’s immune responses. To help CAR T-cell therapy work better on pancreatic tumors, it may be used in combination with antibodies that target PD-1 or PD L-1, the checkpoint antigen on some tumor and normal cells to which PD-1 binds.

Other T-cell therapies

A related form of T-cell transfer therapy is called TIL therapy, which stands for tumor infiltrating lymphocyte therapy. T-cells removed from the blood are analyzed to see which are best able to recognize and attack cancer cells. A large number of these cells are then grown in the lab and infused back into the body in the hopes of generating a more robust immune response.

T-cell receptor therapy, or TCR therapy, manipulates the T-cells so that they express a certain receptor. It differs from CAR T-cell therapy in two ways:

  • The receptors are natural, not lab-made.
  • CARs can only find antigens on tumor cell surfaces, while TCRs can find antigens both on the inside and outside of tumor cells.

Cancer vaccines and related treatments

Cancer treatment vaccines involve injecting patients with copies of an antigen known to be on the surface of their cancer cells, spurring the immune system to attack the cells and remember the antigen and recognize it for future attacks. Some vaccines are made with known antigens. Others are made from a patient’s tumor cells, creating a personalized treatment. Since these vaccines rely on a strong immune response, they may not work as well in people with immune systems weakened by cancer treatments, including chemotherapy and radiation therapy.

Cancer vaccines usually are only available by joining a clinical trial. They generally don’t work as well in treating advanced cancer and large tumors, but researchers are studying their efficacy in combination with other immunotherapies.

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