Checkpoint Blockade Immunotherapy

Checkpoint blockade immunotherapy is an innovative cancer treatment that uses a class of drugs known as immune checkpoint inhibitors. Much like other immunotherapies, the goal of checkpoint blockade immunotherapy is to strengthen the body’s immune system and enhance its ability to fight off harmful invaders. Specifically, immune checkpoint inhibitors are designed to help the immune system recognize, target and destroy cancerous cells.

How does the immune system fight cancer?

The immune system has several key components:

• T cells – Certain white blood cells (lymphocytes) help fight off infection by attacking foreign cells that do not belong in the body.
• Antigens – Distinctive protein molecules are found on the surface of different cells.
• Immune checkpoint proteins – Modulators temper the immune system to help prevent an overly robust immune response.

Healthy cells and harmful invaders—such as bacteria, viruses and some cancerous cells—have different antigens, which serve as identification markers for T cells. As such, the T cells use the antigens to distinguish harmless cells that belong in the body from potentially harmful cells that must be destroyed.

The critical role of checkpoint proteins

T cells carry protein molecules, such as immune checkpoint proteins, which help regulate the body’s immune response. Their job is to stop a T-cell attack on harmful cells once the threat is eliminated. This function is critical because an uncontrolled immune response can cause potentially serious inflammatory tissue damage and trigger autoimmune diseases.

Some tumors exploit the immune system’s checkpoint safeguards by tricking them into misidentifying cancerous cells as healthy cells and thus preventing a T-cell attack or halting an attack before the cancerous cells are fully destroyed. This may allow a tumor to continue to grow and spread throughout the body.

How do immune checkpoint inhibitors work?

Immune checkpoint inhibitors are drugs that block checkpoint proteins, effectively “releasing the brakes” on the immune system and bolstering its ability to fight cancer. First approved by the U.S. Food and Drug Administration (FDA) for treating melanoma, ipilimumab (Yervoy®) blocks the immune checkpoint protein CTLA-4 and has improved the survival of patients with the most aggressive form of skin cancer.

Pembrolizumab (Keytruda®) and nivolumab (Opdivo®) are FDA-approved immune checkpoint inhibitors that were developed to block the immune checkpoint known as programmed death receptor-1 (PD-1). These immune checkpoint inhibitors can be used to treat several types of cancer, including:

• Bladder cancer
• Breast cancer
• Head and neck cancers
• Hodgkin’s lymphoma
• Kidney cancer
• Melanoma
• Non-small cell lung cancer

Atezolizumab (Tecentriq®), avelumab (Bavencio®) and durvalumab (Imfinzi®) are other FDA-approved immune checkpoint inhibitors that were developed to block the immune checkpoint PD-L1. These immune checkpoint inhibitors can be used to treat several types of cancer, including:

• Bladder cancer
• Breast cancer
• Merkel cell carcinoma
• Non-small cell lung cancer

Currently, not all types of cancer can be treated with checkpoint blockade immunotherapy. Some tumors that have proven to be resistant to checkpoint inhibitors include prostate cancer, glioblastoma (brain tumors) and pancreatic cancer. Moreover, the results of this type of immunotherapy can vary from one patient to another, even if both have the same type of cancer.

Still, the use of immune checkpoint inhibitors is considered to be a major advancement in cancer treatment, and researchers continue to finetune checkpoint blockade therapy to improve its effectiveness. One approach currently under study is the combined use of immune checkpoint inhibitors and other immunotherapy treatments, such as cancer vaccines andcellular immunotherapy.

Checkpoint blockade immunotherapy vs. chemotherapy

Immune checkpoint inhibitors are generally less toxic and easier on the body than most chemotherapy drugs, which directly target cancerous cells. Additionally, unlike some chemo drugs, immunotherapy drugs do not require an administration port, which is a small disc that is surgically placed in the body to serve as an entry point for the intravenous medications. Immune checkpoint drugs also do not require any pretreatment preparation, such as hydration therapy.

What to expect with checkpoint blockade immunotherapy

Immune checkpoint inhibitors are administered via a vein in an arm (intravenously). Each treatment session takes approximately 30 to 60 minutes. The number of sessions can vary depending on the type of cancer being treated and the drug used in the treatment.

Side effects of checkpoint blockade immunotherapy

Common side effects of immune checkpoint inhibitors include:

• Fatigue
• Loss of appetite
• Nausea
• Diarrhea
• Constipation
• Coughing
• Skin rash
• Joint and muscle pain

Rare but serious side effects can include:

Infusion reactions

While receiving checkpoint blockade immunotherapy, some people experience an infusion reaction, which is similar to an allergic reaction. The symptoms can include fever, chills, facial flushing, itchy skin, dizziness, wheezing and difficulty breathing.

Autoimmune reactions

By targeting a checkpoint protein, an immune checkpoint inhibitor essentially removes a natural safeguard in the body’s immune system. Sometimes, the immune system responds by attacking other parts of the body, such as the lungs, intestines, liver, hormone-producing glands, kidneys and or other vital organs.

The role of checkpoint blockade immunotherapy at Moffitt Cancer Center

Every cancer patient is unique and requires personalized care. Treatment options can vary depending on a patient’s diagnosis and other individual factors. Many patients benefit from a combination of therapies, including checkpoint blockade inhibitors, cellular immunotherapy, radiation therapy and/or chemotherapy.

Cellular immunotherapy is a very active area of research at Moffitt, and we continue to make great strides in increasing its effectiveness and expanding its use in cancer treatment. Our outstanding research program is widely acclaimed and has received national recognition in the form of a Comprehensive Cancer Center designation from the National Cancer Institute. Additionally, our cancer specialists incorporate cellular immunotherapy in treatment plans for their patients as appropriate. Some examples include:

CAR T-cell therapy

Chimeric antigen receptor (CAR) T-cell therapy involves harvesting a patient’s T cells, genetically modifying them to recognize the unique proteins present on the surface of certain cancer cells and then infusing them back into the patient’s body. The modification unleashes the patient’s natural ability to destroy the cancerous cells while leaving the healthy cells intact. CAR T-cell therapy is FDA-approved for patients with certain types of blood and bone marrow cancers.

TCR therapy

Also known as T-cell receptor gene therapy, TCR therapy has shown promise in clinical trials and recently received FDA approval as a therapeutic agent for certain types of cancerous tumors. It is similar to CAR T-cell therapy in that it involves collecting T lymphocytes from a patient’s blood, genetically modifying them and then returning them to the patient. However, the method of modifying the lymphocytes differs between the two immunotherapies.

TIL therapy

Tumor-filtrating lymphocyte (TIL) therapy bolsters the ability of T cells collected from a cancerous tumor to destroy the tumor itself. Generally, TIL therapy involves harvesting lymphocytes and growing them in a laboratory until they have multiplied into billions, then re-infusing them into the patient.

Talk with a cancer expert at Moffitt

Moffitt is a nationally ranked cancer center that delivers care in new and transformative ways. Our patients have access to checkpoint blockade immunotherapy and other advanced treatments as well as our robust clinical trials program. Taking a multispecialty approach to cancer treatment, we can match patients with various clinical trials that are appropriate for their unique needs.

If you would like more information about checkpoint blockade immunotherapy, contact Moffitt Cancer Center at 1-888-663-3488 or complete a new patient registration form online. Your cancer diagnosis is our top priority.

References

SinoBiological
National Cancer Institute: Checkpoint Inhibitors
National Cancer Institute: Which Cancers Are Treated With Immune Checkpoint Inhibitors
eCancer.org: Why Are Some Cancers Unresponsive to Checkpoint Inhibitors