Immunotherapy

Immunotherapy brochureTo help you understand and share this information, you can download and print a booklet that summarizes the detailed information in the following sections.

Immunotherapy for lung cancer is a new type of treatment that aims to enhance the body’s immune response and stop the lung cancer from evading the immune system.

Find out more about how the immune system works, how treatments to boost it can help fight lung cancer, and whether participating in a clinical trial using immunotherapy might be a good option for you.

 

What is the immune system?

The following video explains what the immune system is and what it does.

Organs of the immune systemThe immune system is a network of cells, tissues, and organs that work together to protect the body from foreign invaders such as bacteriaA large group of single-cell microorganisms. Some cause infections and disease in animals and humans or virusesA very simple microorganism that infects cells and may cause disease. The key players in defending the body are a specific type of white blood cellA type of blood cell that helps the body fight infection and other diseases called lymphocytes. There are three types of lymphocytes: B cellsA type of white blood cell that circulates in the blood and lymph seeking out foreign invaders, T cellsA type of white blood cell that helps protect the body from infection and may help fight cancer, and natural killer (NK) cellsA type of white blood cell that patrols the body and is on constant alert, seeking foreign invaders.1,2

Lymphocytes grow and develop in the bone marrowThe soft, sponge-like tissue in the center of most bones, thymusAn organ in the chest behind the breastbone that is part of the lymphatic system, in which T lymphocytes grow and multiply, and spleenAn organ on the left side of the abdomen near the stomach that makes lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. They can also be found in clumps throughout the body, primarily as lymph nodesA rounded mass of lymphatic tissue surrounded by a capsule of connective tissue. (Lymph nodes in the neck are called cervical lymph nodes, and those between the lungs in the middle of the chest are known as mediastinal lymph nodes.) Clumps of lymphoid tissue are also found in the appendix, tonsils, and adenoidsA mass of lymphatic tissue located where the nose blends into the throat. The lymphocytes circulate through the body between the organs and nodes via lymphatic vesselsThin-walled tubular structures that collect and filter lymph fluid before transporting it back to the blood circulation and blood vessels. In this way, the immune system works in a coordinated manner to monitor the body for germs and other abnormal cells.3,4

How does the immune system work?

A key feature of the immune system is its ability to tell the difference between the body's own normal cells, or "self," and cells and other substances that are foreign to the body, or "non-self." Every cell in the body carries a set of distinctive proteinsMolecules made up of amino acids that are needed for the body to function properly on its surface. These identifying surface proteins let the immune system know that they are cells that belong to the body.5 They can be compared to the uniforms a football team wears. In the same way the uniform helps the quarterback know who is on his team, the proteins let the immune system know which cells belong in the body.

Healthy cells display normal proteins on their surface. The immune system has learned to ignore normal proteins. If the surface proteins are abnormal, such as when a virus infects cells or when cells become cancerous, they can be recognized by the immune system. Proteins recognized by the immune system are called antigensA protein on the surface of a cell that causes the body to make a specific immune response.5

If a foreignSomething that comes from outside the body substance—such as a bacteria, virus, or tumorAn abnormal mass of tissue that results when cells divide more than they should or do not die when they should cell—is recognized, the immune system kicks in to try to deal with it. It is the “non-self” antigens on the surface of these cells (the other team’s uniform) that the immune system identifies as abnormal. The immune system is great at recognizing bacteria and virus cells, because they "look" very different from healthy cells. On the other hand, tumor cells started as healthy cells and can look a lot like healthy cells. As a result, the body may have a harder time recognizing tumor cells as foreign.5

In other instances, the immune system may recognize a tumor antigen but may be unable to mount a response strong enough to destroy the tumor. As cancers grow they can evolve ways to escape from attack by the immune system. For these reasons, many people with healthy immune systems still develop cancer and cancer still progresses. In many people with cancer, the cancer cells co-exist with immune cells capable of killing the cancer, but the cancer cells hold the immune cells back from working the way they should.3

What is the role of the immune system in cancer?

The following video explains how the immune system fights cancer.

The immune system has two responses that work together to detect and destroy cancer cells: innate immune responseImmune response to a pathogen that involves the pre-existing defenses of the body and adaptive immune response.

NK cell releasing toxinThe innate immune response is the first line of defense. The innate immune system’s normal function is to protect the body from initial invasion by bacteria and viruses, such as when bacteria invade broken skin or viruses land in the throat. The system includes natural killer (NK) cells, a type of lymphocyte that patrols the body and is on constant alert, looking for foreign invaders and abnormal cells. If cells from the innate immune system recognize a cancer cell as abnormal, they can attach to it and immediately release toxic chemicals that kill it. NK cells and other cells of the innate immune system do not need to recognize a specific abnormality on a cell to be able to do their job.6

If the bacteria, viruses, or cancer cells evade the innate response, then the adaptive immune response becomes active. The adaptive immune response recognizes specific abnormalities on cancer cells that make them different from the cells that are naturally found in the body. Though it is more effective than the innate immune response, the adaptive immune response takes longer to become activated. The cells of the adaptive immune response include the other two types of lymphocytes: B cells and T cells.

B cell releasing antibodyB cells are like the body's military intelligence system, seeking out their targets and sending defenses to lock onto them. They react to “non-self” antigens by making proteins called antibodiesA protein made by B cells in response to an antigen, the purpose of which is to help destroy the antigen. Antibodies are proteins that can attach to foreign and abnormal cells and let the body know that they are dangerous. Antibodies can kill cancer cells in several ways, including binding natural killer (NK) cells to the cancer. B cells can create "memory"—they start to make antibodies quickly when they recognize a past antigen.6

T cells are the major cells the body uses to recognize and destroy abnormal cells. Once a foreign antigen or abnormal cancer protein has been recognized by T cells, the T cells rapidly increase in number. An army of T cells can be formed; these T cells are specifically designed to attack and kill cells that have foreign antigens.6

T cell attacking cancer cellThe T cells are like soldiers, destroying the invaders. They are responsible for coordinating the entire immune responseThe activity of the immune system against foreign substances (antigens) and destroying infected cells and cancer cells. T cells can also create memory after an initial response to an antigen. This memory is meant to ensure that the attack on cancer cells can keep going in the long term, for months or longer. The memory also allows for future responses against the specific abnormal antigen on cancer cells, if and when the cancer comes back.6

If the immune system recognizes the lung tumor cells and can destroy them, why are lung tumors able to grow? Research has shown that some tumors enable their own growth by turning off the immune response. Immune responses beyond what is normal or necessary can be toxic, so T cells have many normal methods to dampen themselves down and essentially turn themselves off. This may allow the growth and development of tumor cells despite the presence of T cells with the potential to kill cancer cells. Researchers are working hard to understand exactly how this happens and how best to turn the cancer-killing T cells back on.7

What is immunotherapy?

Biological therapies use substances made from living organisms to treat disease. These substances either already exist in nature or are manmade in a laboratory.

Immunotherapy is considered a type of biological therapyA type of treatment that uses substances made from living organisms to treat disease. It aims to enhance the body’s immune response and stop lung cancers from escaping from the immune system. Immunotherapy is a treatment that strengthens the natural ability of the patient’s immune system to fight cancer. Instead of targeting the person’s cancer cells directly, immunotherapy trains a person’s natural immune system to selectively target and kill cancer cells.8

Immunotherapies do this in one of two ways: (1) by enabling the immune system to mount or maintain a response or (2) by suppressing factors that block the immune response. There are many different types of immunotherapy. Three main types are currently being studied in people with non-small cell lung cancer (NSCLC)A group of lung cancers that are named for the kinds of cells found in the cancer and how the cells look under a microscope; the most common kind of lung cancer: immune checkpoint inhibitors, therapeutic cancer vaccines, and adoptive T cell transfer. Immune checkpoint inhibitors have made the most progress at this time, and the first FDA-approved immunotherapy drugs for lung cancer belong to this group. Immunotherapy is also being studied in small cell lung cancer (SCLC)A fast-growing cancer that forms in tissues of the lung and can spread to other parts of the body.9

What are the different types of immunotherapies?

Three main types of immunotherapies are currently being studied in people with non-small cell lung cancer (NSCLC): immune checkpoint inhibitors, therapeutic cancer vaccines, and adoptive T cell transfer. Immune checkpoint inhibitors have made the most progress at this time, and are the only type of immunotherapy for which there are FDA-approved drugs available to patients. Immunotherapy is also being studied in small cell lung cancer (SCLC), although this research is in earlier phases.9

Immune checkpoint inhibitors

What is an immune checkpoint?

Many lung cancers co-exist with T cells capable of killing the cancer cells. However, the immune system has many normal mechanisms for dampening itself down. The immune system has fail-safe mechanisms that are designed to suppress the immune response at appropriate times in order to minimize damage to healthy tissue. These mechanisms are called immune checkpoint pathways. They are essentially the brakes on the immune system. The PD1/PD-L1 proteins are an example of an immune checkpoint pathway.

The challenge is that cancer cells are able to use these immune checkpoint pathways to lessen the immune response at the wrong times. This may allow cancer cells to thrive.7

How do immune checkpoint inhibitors work?

The immune checkpoint inhibitors work by targeting and blocking the fail-safe mechanisms of the immune system. Their goal is to block the immune system from limiting itself, so that the original anti-cancer response works better.7

What immune checkpoint inhibitors are FDA-approved?

Platinum-based chemotherapies include carboplatin and cisplatin.

There are currently four FDA-approved immune checkpoint inhibitors for treating patients with lung cancer. Three of them, nivolumab (Opdivo®), pembrolizumab (Keytruda®), and atezolizumab (Tecentriq®) treat patients whose NSCLC has already progressed to metastatic disease. One of them, durvalumab (Imfinzi®), treats patients at an earlier stage in order to reduce the risk of the lung cancer progressing.

  • Durvalumab (Imfinzi®):10 Approved for patients with stage III NSCLC whose tumors are not able to be surgically removed and whose cancer has not progressed after treatment with concurrent platinum-based chemotherapy and radiation therapy.
  • ​Nivolumab (Opdivo®):11Approved for patients with metastatic NSCLC whose lung cancer has progressed on or after platinum-based chemotherapy. Patients with EGFR or ALK mutations should have disease progression on FDA-approved therapy for these mutations before receiving this drug.
  • Pembrolizumab (Keytruda®):12,13 Approved for patients with metastatic non-small cell lung cancer (NSCLC) in the following situations:
    • As first-line treatment for patients whose tumors have a high (greater than or equal to 50%) PD-L1 expression Tumor Proportion Score (TPS), as determined by an FDA-approved test, with no EGFR or ALK mutation.  Approximately 30% of patients with newly diagnosed metastatic NSCLC will have tumors with this high level of PD-L1 expression. (The Tumor Proportion  Score (TPS) is the percentage of cancer cells that produce the PD-L1 proteins. The lung cancer tissue is stained with special dyes that mark PD-L1 positive tumor cells. A pathologist counts the number of cells that stain positive and determines the TPS.)
    • For patients whose tumor expresses PD-L1 (TPS greater than or equal to 1%), as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK mutations should have disease progression on FDA-approved therapy for these mutations before receiving this drug.
    • As first-line treatment of patients with metastatic non-squamous NSCLC in combination with the chemotherapy drugs pemetrexed and carboplatin, irrespective of PD-L1 expression.
  • Atezolizumab (Tecentriq®):14 Approved for patients with metastatic NSCLC whose lung cancer has progressed during or after being treated with platinum-containing chemotherapy. Patients with EGFR or ALK mutations should have disease progression on FDA-approved therapy for these mutations before receiving this drug.

Patients with pre-existing autoimmune conditions should discuss these conditions with their doctors. Those who do go on an immune checkpoint inhibitor should be monitored very carefully for autoimmune side effects.15

How are immune checkpoint inhibitors administered?

FDA-approved immune checkpoint inhibitors are given intravenouslyInto or within a vein. Infusion time and schedules vary, depending on the drug. They are given until disease progressionContinued growth or spread of cancer or serious side effects occur.

  • Durvalumab (Imfinzi®) is given intravenously over 60 minutes in a dosage of 10 mg/kg every 2 weeks for no more than 12 months10
  • Nivolumab (Opdivo®) is given intravenously over 30 minutes in a dosage of either 240 mg every 2 weeks or 480 mg every 4 weeks11
  • Pembrolizumab (Keytruda®) is given intravenously over 30 minutes in a dosage of 200 mg every 3 weeks12
  • Atezolizumab (Tecentriq®) is given intravenously  over 60 minutes in a dosage of 1200 mg every 3 weeks14

How well do immune checkpoint inhibitors work?

Patients whose tumors have high levels of PD-L1 expression are more likely to respond to PD-1/PD-L1 therapies. However, even those with tumors that do not express PD-L1 may respond to these treatments.

In research studies of patients with non-small cell lung cancer that have been published to date, approximately 20% overall have responded to immune checkpoint inhibitors. This includes patients who test negative for PD-1 and PD-L1, as well as those who test positive. The response rate may improve as researchers learn how best to use these drugs.16,17

The response may continue after treatment is stopped.Some of the responses to date have been long-term.16,17

Researchers are looking for many ways to increase the number of people who respond to this treatment. In clinical trialsA type of research study that tests how well new medical approaches work in people, they are combining treatments, boosting the immune system, and using other strategies.

How long does it take to see results from therapy with immune checkpoint inhibitors?

Of the approximately 20% of patients in clinical trials with immune checkpoint inhibitors who have responded, most respond within the first couple of months. 16,17,18,19

In a small subset of patients (1%-3%), the tumor on a CT scanA procedure that uses a computer linked to an X-ray machine to make a series of detailed pictures of areas inside the body may seem to get worse at first and then get better, or there may seem to be new areas of tumor. Doctors have coined the term pseudoprogression to describe this situation. One theory of why this happens is that, as the lymphocytes come in to attack a tumor, the tumor gets larger, and then, as they kill cancer cells, the tumor gets smaller again. The current thinking is that the tumors get larger because a large number of the patient’s T cells move into the tumor to clean it up. Therefore, some tumors that look larger on X-raysA type of radiation used in the diagnosis and treatment of cancer and other diseases and scans are larger because the immune system is attacking the cancer, not because the cancer cells are growing.19,20  For the great majority of patients whose scans show worsening of disease after at least a couple of months on immunotherapy, the scans are accurately showing that the immunotherapy is not working. 

In cases like this, the best course of action will likely be based on a number of factors. If the patient’s scan looks worse but the person is feeling fine, the doctor and patient may decide together to do another course of immunotherapy. If the scan looks worse and the person is feeling worse, then it may not make sense to continue with this type of therapy. In this case, the patient may need another kind of therapy to control the symptoms.

What are the side effects of immune checkpoint inhibitors?

The most common side effects seen with durvalumab (Imfinzi®) are cough, fatigue, pneumonitis/radiation pneumonitis, upper respiratory tract infection, difficulty breathing, and rash.10

The most common side effects seen with nivolumab (Opdivo®) are fatigue, rash, musculoskeletal pain, itching, diarrhea, nausea, weakness, cough, dificulty breathing, constipation, decreased appetite, back pain, joint pain, upper respiratory tract infection, and fever.11

The most common side effects seen with pembrolizumab (Keytruda®) are fatigue, musculoskeletal pain, decreased appetite, itching, diarrhea, nausea, rash, fever, cough, difficulty breathing, and constipation.12

The most common side effects seen with atezolizumab (Tecentriq®) are fatigue, decreased appetite, difficulty breathing, cough, nausea, musculoskeletal pain, and constipation.14

An immune checkpoint inhibitor side effect sometimes seen is pneumonitis, which is inflammation of the lung tissues that may lead to difficulty breathing if not treated early and correctly.  Pneumonitis and some of the other side effects seen with immune checkpoint inhibitors are related to “turning on” the immune system, which then may also attack some healthy cells and cause inflammation. Other examples of this include:11,12,14

  • ArthritisA disease that causes inflammation and pain in the joints
  • ColitisAn illness that causes pain and swelling in the colon
  • HepatitisDisease of the liver causing inflammation
  • NephritisAcute or chronic inflammation of the kidney caused by infection, degenerative process, or vascular disease and renal dysfunction
  • Inflammation of the endocrine glandsA gland (for example, the thyroid or the pituitary) that produces an endocrine secretion, like the thyroid

Inflammation of the thyroid can cause either high or low thyroid hormone levels (hyperthyroidism or hypothyroidism). Inflammation of the liver can also occur, so liver function tests may be run periodically to check for that. Inflammation-related side effects are usually easy to manage, but sometimes patients may need to take additional medications, including corticosteroids or thyroid hormone replacement.11,12,14

Because these drugs have been studied in patients for only a few years, it is not known for certain what the long-term side effects are in patients with profound responses, including remission of cancer. However, doctors have some ideas about what they may be:11,12,14,21

  • If it affects the endocrine gland, a patient may need thyroid hormone supplementation for the rest of his or her life
  • Some patients develop diabetes and need to be on medication

Some patients experience side effects that are severe enough that they need to stop taking the immunotherapy treatment. In general, based on what has been seen to date, these kinds of treatments are well tolerated by most patients. 

It’s important for patients to tell their doctor if they were ever treated with immunotherapy, even a long time ago, because side effects can show up after long periods of time.

There currently is no way to predict who will and won’t get these side effects. Patients should tell the doctor or nurse if they do experience any side effects  so it can be determined whether the side effects are related to treatment or not. What side effects are being experienced may impact future treatment plans.

For tips on managing treatment-related side effects, visit the Survivor Resource Center.

Where do the immune checkpoint inhibitors fit in the treatment plan for lung cancer?

Durvalumab (Imfinzi®) is currently FDA-approved for patients with stage III NSCLC whose tumors can not be surgically removed and whose disease has not progresed following concurrent platinum-based chemotherapy and radiation therapy.10 

The other three FDA-approved immune checkpoint inhibitors are currently approved for patients with metastatic NSCLC. While all three are indicated for second-line treatment under certain conditions, only pembrolizumab (Keytruda®) is indicated under certain conditions for first-line treatment as well:

Nivolumab (Opdivo®) is currently approved in the second-line setting for treating patients with metastaticHaving spread from the primary site, or place where it started, to other places in the body NSCLC who have been or are being treated with platinum-based chemotherapyTreatment with drugs that kill cancer cells NSCLC whose lung cancer has progressed on or after platinum-based chemotherapy. Patients with EGFR or ALK mutations should have disease progression on FDA-approved therapy for these mutations before receiving this drug.11

Pembrolizumab (Keytruda®) is currently approved for first-line treatment of patients with metastatic non-small cell lung cancer whose tumors express PD-L1 at a high level (Tumor Proportion Score [TPS] greater than or equal to 50%), as determined by an FDA-approved test. It is also approved for second-line treatment for patients with tumors that express PD-L1 with a TPS of greater than or equal to 1% who have disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK mutations should have disease progession on FDA-approved therapy for these mutations before receiving this drug. Finally, it is approved for first-line treatment of patients with metastatic non-squamous NSCLC in combination with the chemotherapy drugs pemetrexed and carboplatin, irrespective of PD-L1 expression.12

Atezolizumab (Tecentriq®) is currently approved as second-line treatment for patients with metastatic NSCLC whose lung cancer has progressed during or after being treated with platinum-containing chemotherapy. Patients with EGFR or ALK mutations should have disease progression on FDA-approved therapy for these mutations before receiving this drug.14

Numerous immune checkpoint inhibitor drugs are currently being tested, including:9

Generic Name Brand Name Types of lung cancer
being studied
Ipilimumab Yervoy® NSCLC, SCLC
Durvalumab` Imfinzi® NSCLC, SCLC
Avelumab  To be determined NSCLC
Tremelimumab To be determined NSCLC
PDR001 To be determined  NSCLC
REGN2810 To be determined NSCLC

Learn more about clinical trials here.

Therapeutic cancer vaccines

What is a therapeutic cancer vaccine?

When most people think of a vaccine, they think of a traditional vaccine given to prevent an infectious disease such as measles or polio. In addition to the traditional vaccines, there are two types of cancer vaccines. A preventive cancer vaccine is given to prevent cancer from developing in healthy people. For example, the hepatitis B vaccine is given to children to protect against a hepatitis B viral infection, which can lead to liver cancer. In contrast, a therapeutic cancer vaccine is given to treat an existing cancer by causing a stronger and faster response from the immune system. Most commonly, they are used in patients in remission in an attempt to prevent likely relapseThe return of a disease or the signs and symptoms of a disease after a period of improvement or the cancer from returning.3,8,22 Therapeutic cancer vaccines are being studied in lung cancer patients.

How do therapeutic cancer vaccines work?

Cancer vaccineA therapeutic cancer vaccine is made from a patient’s own tumor cells or from substances taken from the tumor cells. They are designed to work by activating the cells of the immune system to recognize and act against the specific antigen on the tumor cell. Because the immune system has special cells for memory, the hope is that the vaccines will also help keep the lung cancer from coming back.3,22,23

There are currently no FDA-approved therapeutic cancer vaccines for patients with lung cancer.

How is a therapeutic cancer vaccine administered?

Therapeutic cancer vaccines are given as an injection either right below the skin’s top layer (intradermally), beneath the skin (subcutaneously), or into the muscle (intramuscularly). Early on in the study, the vaccines are given from one to three times a week. The doses are then spread out to every other week and, eventually, to every other month. The studies range from 1 to 3 years.9

Types of injections

Results of therapeutic cancer vaccine administration

Several studies have suggested that the effectiveness of therapeutic cancer vaccines may be enhanced when they are administered along with other formers of cancer therapy. It is also possible that they  may increase the effectiveness of the other treatments themselves. There is also some evidence indicating that surgical removal of the tumor prior to administration of a cancer vaccine may make it easier for the immune system to develop an effective response.22

Where do therapeutic cancer vaccines fit in a lung cancer treatment plan?

While there are no FDA-approved therapeutic cancer vaccines for lung cancer patients, therapeutic cancer vaccines are being studied in clinical trials for both small cell and non-small cell lung cancer. They are being investigated as first-line therapy, second-line therapyTreatment that is usually started after the first set of treatments doesn’t work, has stopped working, or has side effects that are not tolerated, and maintenance therapyTreatment that is given to help keep cancer from coming back after it has disappeared following the initial therapy. They are being tested alone and in combination with chemotherapy and radiation therapy.9

Included among therapeutic cancer vaccines being studied in lung cancer are:9

Generic Name Brand Name  Types of lung cancer
being studied
Tergenpumatucel-L HyperAcute® NSCLC
BI1361849 To be determined NSCLC
CIMAvax-EGF To be determined NSCLC
GV1001 To be determined NSCLC
TG4010 To be determined NSCLC
BEC2 To be determined SCLC
INGN To be determined SCLC

What side effects have been seen in clinical trials?

Inflammation at the site of the injection is the most commonly reported side effect of therapeutic cancer vaccines; this includes redness, pain, swelling, warming of the skin, itchiness, and/or a rash. Also reported are flu-like symptoms, including fever, chills, weakness, dizziness, nausea or vomiting, muscle ache, fatigue, headache, and occasional breathing difficulties.22

More serious health problems have been reported in a smaller number of people after receiving a therapeutic cancer vaccine, but these may not have been caused by the vaccine. They include asthma, appendicitis, pelvic inflammatory diseaseA condition in which the female reproductive organs are inflamed. It may affect the uterus, fallopian tubes, ovaries, and certain ligaments, and certain autoimmune diseases, including arthritis and systemic lupus erythematosus (SLE)A chronic, inflammatory, connective tissue disease that can affect the joints and many organs, including the skin, heart, lungs, kidneys, and nervous system. Rarely, severe allergic reactions to specific vaccine ingredients have been seen following vaccination.22

For tips on managing treatment-related side effects, visit the Survivor Resource Center.

Adoptive T cell transfer

Adoptive T cell transferWhat is adoptive T cell transfer?

The goal of adoptive T cell transfer is to improve the ability of a person’s own T cellsA type of white blood cell to fight cancer.  For lung cancer, this approach is still being developed.

A sample of T cells is removed from the patient and then genetically changed in order to make the T cells more active against specific cancer cells. Scientists can change what is on the surface of the T cells. For example, they can add a receptor to the surface of the T cell that will target a specific antigen on a cancer cell. The receptors work like very specific Velcro that allows T cells to stick to cancer cells and kill the cells. The T cells are then returned to the patient and the altered T cells quickly home in on their targets.8

How does adoptive T cell transfer work?

Typically during an immune response, T cells multiply. After the initial response, most of the newly made T cells are eliminated. This keeps the total T cell number in the body at a normal level. The normal level of T cells is usually not high enough to sustain a response strong enough to effectively fight cancer.8

However, there is evidence that T cells have the ability to multiply in abundance when given to someone whose immune system has been weakened. Therefore, in an adoptive T cell transfer, patients are given chemotherapy prior to the adoptive T cell transfer in order to suppress their immune system. Once the chemotherapy is completed and the immune system is weakened, billions of modified T cells are reintroduced into the patient. The goal of the T cell transfer is to enable the immune system to attack the tumors in a large number that is otherwise impossible and in a way that it is incapable of doing on its own.24

 how are t cells removed from and returned to a patient?

The three ways of performing adoptive T cell transfer are:24,25

  • Taking T cells from the body and changing them with special receptors, called chimeric antigen receptors (CARs). CARs recognize specific proteins found on the surface of cancer cells. The CAR T cells then bind to the cancer cells that have those proteins and destroy them
  • Collecting a sample from the actual tumor and multiplying the T cells in a laboratory
  • Taking T cells from the bloodstream through a procedure called leukapheresisRemoval of the blood to collect specific blood cells; the remaining blood is returned to the body and genetically altering them to attack cancer cells that have specific antigensA protein on the surface of a cell that causes the body to make a specific immune response

After any of these, the T cells are then returned to the patient through an infusionA method of putting fluids, including drugs, into the bloodstream.24

Results of clinical trials involving adoptive T cell transfer

Clinical trials with very strong patient response, including lasting remissions, have led to FDA approval of two CAR T-cell therapies, one for a type of lymphoma and the other for a type of leukemia.26, Whether T cell therapy will eventually prove to be as effective in lung cancer is unknown.

Where does adoptive T cell transfer fit in the treatment plan for lung cancer?

There are no FDA-approved adoptive T cell transfer treatments yet for lung cnacer, but clinical trials are being conducted among lung cancer patients.

What side effects have been seen in clinical trials?

Among the most common side effects of adoptive T cell transfer is the serious cytokine-release syndrome; this is a rapid and large-scale release of cytokinesA type of protein that is made by certain immune and non-immune cells and has an effect on the immune system into the bloodstream. Cytokines are chemical messengers that help the T cells carry out their duties. Too many cytokines can lead to high fevers and quick drops in blood pressure. In many patients, this side effect can be managed with standard supportive treatments, including steroids.24,26

Other serious side effects include neurotoxicity—changes in the brain from the treatment that can result in headaches, seizures and confusion; infections, low blood cell counts, and a weakened immune system.26

For tips on managing treatment side effects, visit the Survivor Resource Center.

What clinical trial options are available?

As noted, there are a number of clinical trials under way in lung cancer patients for the different types of immmunotherapy treatments.9

If you are considering participating in a clinical trial, start by asking your doctor whether there is one for which you might qualify in your area. In addition, here are several resources to help you find one that may be a good match for you:

Learn more about clinical trials here.

Questions to ask about clinical trials

Print this list

  • What are the benefits and risks of participating in an immunotherapy clinical trial?
  • How will I be monitored while participating in a clinical trial?
  • What are my responsibilities during the clinical trial?
  • Are there any costs associated with my participation in a clinical trial?
  • Where can I learn more about clinical trials?
  • Who can I speak with if I have questions during the clinical trial?
  • What happens if I decide I do not want to participate in the clinical trial at some point?

Updated March 8, 2018


References

  1. What is the Immune System? Vaccines.gov website. https://www.vaccines.gov/basics/prevention/immune-system/index.html. Syndicated May 11, 2017. Accessed December 8, 2017. 
  2. Lymphocytes. US National Library of Medicine website. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0022042/. Accessed December 6, 2017.
  3. Cancer and the Immune System: The Vital Connection. Cancer Research Institute website. http://www.cancerresearch.org/CRI/media/PDF-content/Cancer-and-the-Immune-System-2016-final-print.pdf. Revised 2016. Accessed December 8, 2017.
  4. Lymphatic Vessels. US National Library of Medicine website. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0022680/. Accessed December 8, 2017.
  5. Learning About the Immune System. Leukine-Sanofi Oncology website. http://www.leukine.com/patient-learning-about-the-immune-system. Accessed December 8, 2017.
  6. Humphrey J, Perdue S. Immune System. Britannica website. https://www.britannica.com/science/immune-system. Accessed December 8, 2017.
  7. Pardoll D. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012; 12:252-264. doi:10.1.1038/nrc3239. http://www.nature.com/nrc/journal/v12/n4/full/nrc3239.html. Accessed December 8, 2017.
  8. Biological Therapies for Cancer. National Cancer Institute website. https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/bio-therapies-fact-sheet. Reviewed June 12, 2013. Accessed December 8, 2017.
  9. Clinicaltrials.gov. US National Institutes of Health website. http://clinicaltrials.gov. Accessed December 8, 2017.
  10.  Imfinzi®) (durvalumab) injection [package insert]. Astra-Zeneca Pharmaceuticals LP.  Wilmington, DE; February 2018. https://www.azpicentral.com/imfinzi/imfinzi.pdf. Revised February 2018. Accessed February 23, 2018.
  11. Opdivo® (nivolumab) injection [package insert]. Bristol-Myers Squibb Company. Princeton, NJ; March 2015. http://packageinserts.bms.com/pi/pi_opdivo.pdf. Revised March 2018. Accessed March  8, 2018.
  12. Keytruda® (pembrolizumab) injection [package insert]. Merck & Co., Inc. Whitehouse Station, NJ; 2014. http://www.merck.com.product/usa/pi_circulars/k/keytruda_pi.pdf. Revised May 2017. Accessed December 8, 2017.
  13. Guide to PD-L1 Expression Testing in NSCLC. Merck & Co., Inc. https://www.keytruda.com/static/pdf/keytruda-pd-l1-expression-testing-guide.pdf. Published October 2017. Accessed December 8, 2017.
  14. Tecentriq® (atezolizumab) injection [package insert]. Genentech, Inc., South San Francisco, CA; 2016. https://www.gene.com/download/pdf/tecentriq_prescribing.pdf. Posted October 2016. Accessed December 8, 2017.
  15. Immunotherapy in Patients with Active Autoimmune Disease. ASCO-SITC Clinical Immuno-Oncology Symposium Daily News. https://immunosym.org/daily-news/immunotherapy-patients-active-autoimmune-disease. Posted February 16, 2017. Accessed January 11, 2018.
  16. Helwick C. Strong Showing for Anti-PD-1 Agents in Non-Small Cell Lung Cancer. The ASCO Post website. Volume 5. Issue 11. https://www.ascopost.com/issues/july-10-2014/strong-showing-for-anti-pd-1-agents-in-non-small-cell-lung-cancer. Posted July 10, 2014. Accessed December 8, 2017.
  17. Chustecka Z. ‘Exciting Times’ With Immunotherapy in Lung Cancer. Medscape Medical News website. http://www.medscape.com/viewarticle/813526. Posted October 31, 2013. Accessed December 8, 2017.
  18. Garon, E. Time to Response to Immunotherapy and the Concept of Pseudoprogression. Global Resource for Advancing Cancer Education website. http://cancergrace.org/lung/files/2015/12/GCVL-LU-Immunotherapy_Response_Time_and_Pseudoprogression-Concept.pdf. Posted December 15, 2015. Accessed January 10, 2018.
  19. Harvey RD. Immunological and Clinical Effects of Targeting PD-1 in Lung Cancer. Clinical Pharmacology & Therapeutics.  2014 Aug; 96(2): 214-223. doi:10.1038/clpt.2014.74. http://onlinelibrary.wiley.com/doi/10.1038/clpt.2014.74/full. http://onlinelibrary.wiley.com/doi/10.1038/clpt.2014.74/full. Published April 1, 2014. Accessed December 8, 2017.
  20. West, H. Death by "Pseudo-progression": Knowing When to Cut Your Losses with Immunotherapy. Global Resources for Advancing Cancer Education website. http://cancergrace.org/lung/2016/09/12/death-by-pseudo-progession-knowing-when-to-cut-your-losses-with-immunotherapy/#more-17624. Posted September 12, 2016. Accessed December 8, 2017.
  21. Corsello S, Barnabei A, et al. Endocrine Side Effects Induced by Immune Checkpoint Inhibitors. The Journal of  Clinical Endocrinology & Metabolism. Volume 98, Issue 4, 1 April 2013, pages 1361-1375. https://doi.org/10.1210/jc.2012-4075. Published Apil 1, 2013. Accessed December 8, 2017.
  22. Cancer Vaccines. National Cancer Institute website. https://www.cancer.gov/about-cancer/causes-prevention/vaccines-fact-sheet. Reviewed December 18, 2015. Accessed December 8, 2017.
  23. Cancer Vaccines. American Cancer Society website. https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/cancer-vaccines.html. Reviewed August 8, 2016. Accessed December 8, 2017.
  24. CAR T-Cell Therapy: Engineering Patients' Immune Cells to Treat Their Cancers. National Cancer Institute website. http://www.cancer.gov/about-cancer/treatment/research/car-t-cells#side%20effects. Updated December 14, 2017. Accessed January 11, 2018.
  25. Balch CM, Kaufman HL (eds). Understanding Cancer Immunotherapy, Third Edition. Overland Park, KS. Society for Immunotherapy of Cancer (SITC) and PRP Patient Resource Publishing, 2016. http://www.patientresource.com/userfiles/file/Immunotherapy2016.pdf. Accessed December 8, 2017.
  26. CAR-T-Cell Therapies. American Cancer Society website. ttps://www.cancer.org/treatments/treatments-and-side-effects/treatment-types/immunotherapy/car-t-cell1.html. Revised October 31, 2017. Accessed January 11, 2018.

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