Overview of Chimeric Antigen Receptor T-Cell Therapy
Chimeric antigen receptors (CARs) are laboratory-engineered receptors. These receptors can recode and enhance the abilities of T-lymphocytes, cells which are a crucial part of our immune system. The idea behind using CARs in cancer treatments is that they can be designed to specifically target proteins found on cancer cells, allowing them to rapidly produce many identical, cancer-fighting cells.
These specially designed cells can be directly added to the patient’s body, making the process quicker than waiting for the body to naturally develop its own response. This is different than typical immune responses which use direct antibodies. Instead, these supercharged T-cells works like a medication, fighting off cancer cells and potentially providing both immediate and long-term protection against cancer.
Why do People Need Chimeric Antigen Receptor T-Cell Therapy
Chimeric antigen receptors, or special proteins used in certain cancer treatments, are composed of several parts: a part outside the cell that sticks to cancer cells, a component inside the cell that activates the body’s own defense system (T-cells), and a part that allows these two sections to communicate. Tisagenlecleucel is a type of treatment that uses these receptors to aid the body’s defense system in identifying and eliminating cancerous cells. This works by taking a patient’s own T-cells and genetically modifying them to recognize a protein (CD19) that is present on both cancerous and noncancerous cells. Once the modified T-cells bind to the CD19 protein, they get activated and start to eliminate the harmful cells.
Axicabtagene ciloleucel is another similar treatment that targets the CD19 protein. Once the special protein on the T-cells binds to the CD19 protein on a cancer cell, it trigger a series of events that end up with the cancer cell being killed.
Currently, both these treatments target the protein CD19 found on B lymphocytic cells, a type of white blood cell that plays a role in the immune response. These current treatments are used for certain types of blood cancers. However, research is being done to investigate how this technology can be used to target other types of cancers. Some potential targets being researched include proteins commonly found on lung cancer, glioblastoma (a type of brain tumor), breast cancer, and prostate cancer cells, to name a few.
When a Person Should Avoid Chimeric Antigen Receptor T-Cell Therapy
According to the information provided with the medications, there are no specific reasons or situations where these drugs shouldn’t be used. However, extra care should be taken for patients suffering from autoimmune disorders (diseases where the body’s immune system attacks its own cells) and those who have undergone organ transplants. This is because these medical circumstances might affect how the patient responds to the medication.
Equipment used for Chimeric Antigen Receptor T-Cell Therapy
When giving CAR-T cell treatments, which are therapies that engineer your own cells to fight cancer, it’s critical to make sure the patient’s name matches the name on the infusion bag. This is because these therapies are made specially for each individual patient. Instead of using a leuodepleting filter, which is a device that reduces the number of white blood cells, it’s preferable to use a method called central venous access. This is where medication is delivered directly into a large vein close to your heart.
It’s also necessary to have certain medicines and equipment on hand before the infusion begins, and throughout the recovery period, just in case any side effects occur. These include medications like tocilizumab or siltuximab, which are Interleukin-6 antagonists that work to block a protein that can cause inflammation. Corticosteroids, which are medicines that reduce inflammation, are also needed. Emergent equipment, which includes the tools and devices needed to handle emergencies, should also be readily available.
Who is needed to perform Chimeric Antigen Receptor T-Cell Therapy?
Both these medicines need to be given at a certified health care center. It’s very important that the patient is checked daily for a week after they get the medicine. The medical team will look for any signs of CRS (a reaction to the medicine that can cause fever, fatigue, and other symptoms) and CRES (a reaction that can affect the brain). We also advise the patient to stay close to the health care center for about 4 weeks after getting the medicine.
Possible Complications of Chimeric Antigen Receptor T-Cell Therapy
CAR T-cell therapy is a type of treatment often used for serious diseases, and the two most common side effects are the cytokine-release syndrome (CRS) and neurological issues known as CAR-related encephalopathy syndrome (CRES).
Cytokine-release syndrome is the most frequent side effect from CAR T-cell therapy. A person with CRS may have a high fever, low blood pressure, and hypoxia (which means the body or a part of the body has a lack of oxygen). They could also experience toxicity in multiple parts of their body, such as the heart, stomach, lungs, kidneys, blood, and nervous system. This side effect tends to start in the first week after the CAR T-cell therapy, reaching its peak within one to two weeks. When treating CRS, health care professionals consider factors such as temperature, blood pressure, oxygen saturation, and whether other organs are affected. They typically use methods like supportive care (like medication for fever, intravenous fluid for dehydration or low blood pressure, or additional oxygen for hypoxia), corticosteroids (which are medications that reduce inflammation), and medications known as Interleukin-6 antagonists.
The second common side effect, CAR-related encephalopathy syndrome, shows up as symptoms that look like a condition known as toxic encephalopathy. People with CRES may have trouble paying attention, difficulties with language, and issues with handwriting. They could also have confusion, agitation, difficulty speaking, excessive sleepiness, or trembling. Unlike CRS, it’s not fully understood why CRES happen. This condition normally starts in the first five days after the CAR T-cell therapy. In case of CRES, doctors will adjust the treatment depending on the severity of your symptoms (based on a test called the CARTOX-10), your blood pressure, and whether you have seizures or weakness. Treatment normally involves supportive care, corticosteroids, and Interleukin-6 antagonists, similar to CRS treatment. Doctors also often recommend lifting the head of a patient’s bed to reduce the risk of accidentally inhaling food or drink and to boost blood flow in the brain. Consulting with a neurologist, who can monitor and evaluate the condition, can also be helpful.
Additional side effects could include symptoms like fever, exhaustion, lack of appetite, and joint pain. Neurological issues like headaches, altered consciousness, hallucinations, and tremors can occur. People may also experience liver issues, abnormal blood conditions, heart problems, respiratory issues, kidney problems, gastrointestinal issues like nausea and vomiting, and muscle issues like aching or weakness.
What Else Should I Know About Chimeric Antigen Receptor T-Cell Therapy?
The United States Food and Drug Administration (FDA) approved the first treatment using CAR-T cells, a type of immune cell that’s genetically engineered in a lab to attack cancer cells, in August 2017. This treatment is called tisagenlecleucel. It is used in young patients, up to 25 years old, who have a specific type of leukemia (a blood cancer) known as B-cell precursor acute lymphoblastic leukemia, that is hard to treat or has come back after treatment. It is also used in treating adult patients with a kind of lymphoma, another type of blood cancer, called large B-cell lymphoma if it returns or remains after two or more treatments. This includes types such as diffuse large B-cell lymphoma, high-grade B-cell lymphoma, and the type that develops from a different condition called follicular lymphoma.
In October 2017, the FDA approved another CAR-T cell therapy called axicabtagene ciloleucel. This treatment is also used for adult patients who have large B-cell lymphoma that comes back or continues after two or more different treatments. This includes conditions like diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and that developing from follicular lymphoma.
It’s important to know that neither of these treatments is recommended for patients with lymphoma that starts in the central nervous system, which includes the brain and spinal cord. However, researchers are still studying the use of CAR-T cell treatments for many different types of cancers. Many clinical trials, which are research studies involving volunteer patients, are underway. They’re testing CAR-T cell treatments on a variety of diseases including multiple myeloma, which is a cancer of plasma cells, central nervous system tumors, and common cancers like those in the liver and lung.
