Types of Immunotherapy

Immunotherapy uses the natural power of your immune system to fight illnesses, including cancer. In the past few decades, it’s become a key part of treatment for many different types of the disease.

But not all immunotherapies work the same way. Some boost your immune system overall, while others try to teach it to attack very specific types of cells found in tumors.

Each has different benefits and risks and is used in different cases.

CAR T-Cell Therapy

CAR T-cell is short for chimeric antigen receptor T-cell therapy. It’s also called adoptive cell transfer therapy, or ACT. It’s only used to treat two types of blood cancers:

  • Tisagenlecleucel (Kymriah) is used to treat children and adults up to age 25 with acute lymphoblastic leukemia (ALL) whose cancer didn’t respond to chemotherapy or who had the disease come back two or more times after treatment.
  • Axicabtagene ciloleucel (Yescarta) is approved to treat adults with some types of large B-cell lymphoma, such as non-Hodgkin's lymphoma, whose cancer didn’t respond to other treatments or who had the disease come back after those treatments.

T cells are a type of white blood cell your immune system makes to fight disease. Antigens are foreign substances your immune system targets. When your immune system senses antigens in your body, it releases T cells as self-defense.

With CAR T-cell therapy, doctors can “reprogram” your T cells to attack cancer cells. First, you go through a process called leukapheresis that takes a couple of hours. Your doctors take blood out of your body, separate some T cells from other white blood cells, then put your blood back in.

In a lab, technicians add chimeric antigen receptors (CAR) to your T cells so they can seek out and destroy your exact type of cancer cells. This part takes a few weeks because your doctor needs to reprogram a large amount of CAR T cells to do the job.

Before the new T cells are put into your bloodstream, you may need chemotherapy to cut down on the other types of immune cells in your body. This helps clear the path for the T cells to do their work. Once the CAR T cells are ready, your doctor puts them into your bloodstream. CAR T cells multiply, then seek out and destroy your cancer cells.

Because CAR T cells make many copies of themselves to fight your cancer, they can cause serious side effects in some people, like very high fever, severe low blood pressure, confusion, headaches, seizures, a weakened immune system, low blood cell counts, or severe infections.

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TCR Therapy

T-cell receptor therapy (TCR) is another type of ACT used to fight cancer. As with CAR T-cell therapy, doctors take T cells from your blood, then reprogram them so they find cancer cells more easily. But TCRs tell the T cells to look for tiny bits of specific antigens inside your cancer cells.

TCR therapy is done in a similar way as CAR T-cell therapy. T cells are taken from your blood and retooled in the lab. After chemotherapy, your doctor puts the re-engineered T cells back in your body.

Though the FDA hasn’t approved any TCR therapies, some are being tested in people who have certain types of synovial sarcoma (a soft-tissue cancer) and metastatic melanoma. So far, it’s shown mixed results. In some people, it seems to have worked for a few months.

In these small trials, people had different reactions to TCR therapy. Some had no side effects, while others had mild to moderate side effects like diarrhea, fevers, fatigue, rashes, and nausea. Others had more serious reactions, including high fever, dehydration, and graft-versus-host disease.

TIL Therapy

Tumor-infiltrating lymphocytes (TIL) is another type of ACT therapy. Unlike CAR T cells or TCRs, TIL white blood cells are not reprogrammed in a lab. They’re cells made by your immune system. If these cells have gotten inside the cancer cells, it’s a sign that your body is trying to fight the cancer on its own.

First, doctors will take TILs from your tumor tissue and grow a large number of them in a lab. They then turn up their cancer-fighting ability by adding proteins called cytokines. These proteins help your TILs find and destroy cancer cells.

After treatment with chemotherapy to lower the number of other T cells, the TILs are put into your blood in one dose. The idea behind TIL therapy is that this massive amount of “turned up” white blood cells can break through and kill off the tumor.

TILs are being tested in trials of people who have colorectal, kidney, ovarian, or skin cancers like melanoma. Early results have been promising. One big challenge is that it’s hard to get TILs from some people.

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Monoclonal Antibodies

An antibody is a molecule that flags proteins in your body as invaders. It then recruits other parts of your immune system to destroy any cells that contain those proteins. Researchers can make antibodies in the lab. They’re called "monoclonal" antibodies. Different ones work in different ways:

  • Naked monoclonal antibodies, the most common type for cancer treatment, don’t have anything attached to them. They tell your immune system to attack cancer cells or block proteins within tumors that help the cancer grow.
  • Conjugated monoclonal antibodies have a chemotherapy drug or radioactive particle attached to them. The antibodies attach directly to cancer cells. That means they deliver these drugs where they’re needed the most. This lowers side effects and helps treatments like chemotherapy and radiation work their best.
  • Bispecific monoclonal antibodies are designed to bind to two different proteins at once. Some attach to both a cancer cell and an immune system cell, helping promote immune system attacks on the cancer.

Most people get this type of medication through a vein. Your doctor might also pair it with other treatments like chemotherapy or hormone therapy. How often you get it depends on your cancer type. Research is underway to see how monoclonal antibodies work for many cancer types.

Immune Checkpoint Inhibitors

To keep you healthy, your immune system has to spot invading molecules like bacteria and viruses. It also has to know which of your own cells not to attack. To keep control, your immune system has molecular brakes called checkpoints. Cancer cells sometimes take advantage of them by turning them on or off so they can hide. Immune checkpoint inhibitors are drugs designed to release these brakes and let your immune system do its job. They include:

  • PD-1 or PD-L1 inhibitors: They target checkpoints called PD-1 or PD-L1 that are found on T cells in your immune system. These inhibitors treat melanoma, non-small-cell lung cancer, kidney cancer, bladder cancer, head and neck cancers, stomach cancer, colorectal cancer, and Hodgkin's lymphoma.
  • CTLA-4 inhibitors turn off a checkpoint called CTLA-4, which is also found on T cells. These inhibitors are used for melanoma, colorectal, and certain other cancer types.

Since these drugs rev up your immune system, they can cause a range of side effects, including fatigue, cough, nausea, loss of appetite, rash, and problems in your lungs, kidneys, intestines, liver, or other organs.

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Cancer Vaccines

You probably think of a vaccine as something you get to prevent an infection like the flu. But it can be any compound that’s put into your body to start an immune reaction. Vaccines treat cancer by spurring your immune system to attack tumor cells. They can be made of dead cancer cells, proteins or pieces or proteins from cancer cells, or immune system cells. Researchers are working on several right now, but only one is fully approved. Sipuleucel-T (Provenge) is used to treat advanced prostate cancer that doesn’t respond to other treatments.

General Immunotherapies

Other immunotherapies work by boosting the activity of your immune system in general without targeting a tumor. A more active immune system can better fight cancer. General immunotherapies fall into a few different classes of drugs:

  • Interleukins are a type of cytokine, a molecule produced by some immune cells to control the growth and activity of other immune cells. A man-made version of an interleukin called IL-2 is approved to treat advanced kidney cancer and metastatic melanoma. Researchers are studying others.
  • Interferons are a type of cytokine that can change the way your immune system works. An interferon called IFN-alfa is used to treat cancers, including:
    • Hairy cell leukemia
    • Chronic myelogenous leukemia (CML)
    • Follicular non-Hodgkin's lymphoma
    • Cutaneous (skin) T-cell lymphoma
    • Kidney cancer
    • Melanoma
    • Kaposi sarcoma
  • Colony stimulating factors strengthen your immune system by boosting the production of white blood cells in your bone marrow. This can help your immune system return to normal activity after chemotherapy.
  • Other drugs including imiquimod (Zyclara), lenalidomide (Revlimid), pomalidomide (Pomalyst), and thalidomide (Thalomid) kick-start immune system reactions and are used to treat some cancers.
WebMD Medical Reference Reviewed by Laura J. Martin, MD on January 20, 2019

Sources

SOURCES:

American Cancer Society: “Cancer Vaccines,” “Immune checkpoint inhibitors to treat cancer,” “CAR T-cell Therapy,” “Monoclonal antibodies to treat cancer,” “Non-specific cancer immunotherapies and adjuvants,” “What is cancer immunotherapy?” “What’s new in cancer immunotherapy research?”

Disease Models and Mechanisms: “Genetically modified T cells in cancer therapy: opportunities and challenges.”

Immunotherapy: “Current status for engineered T-cell therapy for synovial sarcoma.”

National Cancer Institute: “CAR T-cell Therapy Approved for Some Children and Young Adults With Leukemia,” “Immunotherapy,” “Immunotherapy: Using the immune system to treat cancer.”

Mayo Clinic: “What cancers may be treated with monoclonal antibody drugs?”

Rambam Maimonides Medical Journal: “Adoptive T Cell Immunotherapy for Cancer.”

University of Texas M.D. Anderson Cancer Center: “Immunotherapy.”

FDA: “FDA Approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma.”

New England Journal of Medicine: “T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer.”

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