A number of CAR T-cell therapy products have been approved for use in a number of different malignancies, such as LBCL, B-ALL, and MM. The development of CAR T cells has dramatically changed the treatment of several hematological malignancies and, with longer follow-up, may be curative for a subgroup of patients. For many patients undergoing treatment with CAR-T, this therapy provides significant long-term remissions and, most importantly, allows them to enjoy a good quality of life. CAR-T cell therapy is a cancer treatment that removes cells from the body and genetically modifies them so they can fight cancer.
It is most often used to treat cancers that affect blood cells, such as certain types of leukemia, lymphoma, and multiple myeloma. CAR-T cell therapy stands for chimeric antigen receptor (CAR) T-cell therapy. This treatment falls under the category of immunotherapy. Immunotherapy for cancer takes advantage of the body's immune system to attack cells cancerous.
CAR-T cell production begins with the collection of a person's own T cells. T cells, also known as T lymphocytes, are a type of white blood cell. T cells play a key role in the body's immune system because of their ability to identify and attack cells that don't belong to the body, such as germs and cancer cells. For CAR-T cell therapy, T cells are removed from the blood using a process called leukapheresis.
In the laboratory, these T cells are modified to produce synthetic proteins called chimeric antigen receptors (CARs). The modified cells are called CAR-T cells. The cells are grown in much higher quantities in the laboratory and then re-injected into the person's bloodstream. Synthetic CARs allow T cells to bind to specific proteins called cancer cell antigens.
This attachment activates T cells to kill cancer cells. The death of cancer cells triggers new immune responses against cancer. In addition, CAR-T cells can continue to multiply in the body and produce long-lasting anti-cancer results. This ability to be specific for a particular antigen makes CAR-T cell therapy different from other T cell therapies, such as therapies with T cell receptors and lymphocytes that infiltrate tumors. Tumor-infiltrating lymphocyte (TIL) therapy uses your own white blood cells to fight cancer cells, usually in the context of solid tumors.
In this case, some white blood cells in the body have recognized the cancer cells and have attached themselves to them; there may not be enough of them to overcome the cancer. These white blood cells are called tumor-infiltrating lymphocytes. TIL therapy removes these white blood cells from a section of the cancer that was surgically removed. The cells are grown in a lab and returned to the body to fight cancer.
T-cell receptor therapy (TCR) removes T cells from a person's blood, similar to CAR-T cell therapy. Unlike T cells used in CAR-T cell therapy, T cells used in TCR therapy are designed to express a natural T cell receptor that recognizes proteins inside cancer cells and not just on the surface. TCR therapy has been used to treat solid tumors. TCR therapy can attack antigens that CAR-T cell therapy cannot reach.
CAR-T cell therapy is also different from stem cell transplantation (SCT). Another term for stem cell transplant is bone marrow transplant. People who receive a stem cell transplant receive healthy bone marrow stem cells. When stem cells are donated by another person, this is called allogeneic SCT. When the stem cells used are a person's own cells, it's called autologous SCT.
CAR-T cell therapy is used to treat cancers that affect blood cells. This includes some types of leukemia, lymphoma, and multiple myeloma. CAR-T cell therapy may not be for everyone diagnosed with one of these types of cancer. Talk to your cancer team about the risks and benefits of treatment.
Also, keep in mind that CAR-T cell therapy is evolving for many different types of cancer, sometimes in clinical trials. Ask your team if a clinical trial may be right for you. Like other cancer treatments, CAR-T cell therapy has risks, such as long waiting times and serious side effects that may require hospitalization. Some side effects can be life-threatening, so the health care team closely monitors for these side effects during and after treatment.
You may have to wait up to two months for your T cells to change in the lab. Waiting that long can increase the chances that the cancer will progress. The large number of CAR-T cells in the body after a treatment infusion helps stimulate the immune response. This, in turn, raises levels of inflammation. If severe, cytokine release syndrome can be fatal, although this is rare.
Another rare complication is a second, potentially fatal inflammatory reaction. This can occur in people who have already recovered or who have been treated for cytokine release syndrome. Symptoms include high levels of iron in the blood, low blood cell counts, blood clotting problems, high levels of liver enzymes, and organ failure. This group of symptoms is called a syndrome similar to hemophagocytic lymphohistiocytosis associated with immune effector cells (IEC-HS).
Treatment is available for inflammatory side effects. CAR-T cells are small enough to cross the blood-brain barrier. This barrier is a protective membrane that separates the blood supply to the brain from the rest of the brain tissue. In the brain and central nervous system, activated T cells can cause a group of symptoms known as immune effector cell-associated neurotoxicity syndrome (ICANS).
The most serious forms of ICANS can cause movement problems, seizures and brain inflammation. Treatment is also available for these side effects. After receiving CAR-T cell therapy, you are more likely to get infections. This is because treatment can lower blood cell counts, including white blood cells, weakening the immune system.
Immediately after treatment, people are more likely to get bacterial infections. They usually occur in the first month. The increased risk of viral infections, such as colds or other respiratory illnesses, may persist even for a year after treatment. Serious infections, such as those caused by COVID-19, are also possible. People can get serious fungal infections, but this isn't common. Taking additional steps to minimize the spread of germs can help.
Preventive measures may include frequent hand washing, limiting exposure to sick people, and avoiding raw or raw foods. One of the challenges faced with CAR-T cell therapy is that cancer cells can change over time and adapt to new environments and treatments. For example, cancer cells can produce antigens that are different from those that the treatment is aimed at. Having these other antigens can allow cancer cells to escape the immune system and continue to multiply.
Scientists hope to find treatments that target more than one antigen at a time or that target them in turn. Some people have developed other types of blood or bone marrow cancers within five years of receiving CAR-T cell therapy. However, it's not clear if this was due to CAR-T cell therapy or other treatments they received, such as chemotherapy. Because these advances have been rare, the benefit of CAR-T cell therapy is likely to outweigh the risk of secondary cancer.
CAR-T cell therapy is usually offered at specialized medical centers. If you have a blood cancer that doesn't respond to treatment or has returned, your oncologist may refer you to a hospital that specializes in CAR-T cell therapy. Your CAR-T cell therapy specialist can help you evaluate the risks and benefits of CAR-T cell therapy for your circumstances. You may also be referred to a clinical trial or other treatment that may be more useful for you.
This initial evaluation lasts about a week. If you continue therapy, plan a total treatment time of several months from remission to the end of treatment. You should be close to the hospital at different stages, especially during and after the T cell infusion. This may involve relocating for a time. Often, these hospitals have a team dedicated to helping you with different aspects of CAR-T cell therapy.
This may include obtaining treatment information, obtaining insurance approval, arranging transportation, and finding accommodation. If CAR-T cell therapy is right for you, the next step is to harvest your T cells. For this step, you must go to the hospital where you will be receiving the treatment. This visit is usually outpatient, meaning you don't have to stay in the hospital unless it's necessary for your safety and health. Before this step, your health care team may ask you to stop any treatment that may have a negative impact on T cells, such as chemotherapy, immunosuppressive drugs, or steroids.
The health care team also stops any blood-thinning medications that may increase the risk of bleeding. The process for collecting T cells is called leukapheresis. In some people, cells are removed through a thin, flexible tube called a catheter that is placed in a vein in the arm. For others, the best option is to collect cells through a catheter placed in a large vein in the chest or neck.
The catheter is connected to a machine that filters T cells from the blood that is drawn and returns the rest of the blood to the body. This process can take several hours. Most people can get enough white blood cells during a session. You may feel tired after the procedure, but you should be able to go home after this procedure. Once the T cells are collected, they are sent to a special laboratory. Laboratory professionals modify cells to attack the specific antigen that produces cancer.
The total manufacturing time usually takes about two weeks, although it can take up to a couple of months. While you wait, you may need to undergo what is called transient therapy. This is a treatment such as chemotherapy, immunotherapy, or radiation therapy to minimize cancer growth until the CAR-T cells are lists. Most people can go home while their T cells are changing.
Follow the instructions your healthcare team gives you about how to take care of yourself during this time. Tell your health care team about any new or worsening symptoms or any changes in your health. You can use this time to finalize your plans. The preparation for the infusion, the infusion itself and the care after the infusion are carried out without an intermediate time.
Plan to be close to the treatment hospital for several weeks or months once preparation for the infusion begins. When the CAR-T cells are ready, they are sent back to the treatment center for the infusion process. At this time, you and your caregiver should be close to the treatment hospital. If you don't live nearby, you may need to move closer to the hospital.
About five days before the infusion, the health care team reassesses your health status to make sure you're ready for treatment. The healthcare team also wants to make sure that you're not fighting any active infections. This is so that the treatment doesn't overload the immune system. If you're still a good candidate for therapy, you'll be given chemotherapy every day for three days.
You may hear that this process is known as lymphodepleting chemotherapy. This is done to lower the level of existing T cells and to make room for new CAR-T cells. It also helps to minimize immune system reactions against CAR. Lymphodepleting chemotherapy is usually an outpatient procedure, unless it is hospitalization is necessary.
Be sure to tell your healthcare team if you experience side effects from chemotherapy. There may be treatments that can ease side effects and make you more comfortable. After chemotherapy, you usually have a couple of days to rest. The CAR-T cell team gives you instructions on the steps to take and when to use the infusion.
On the day of the infusion, your CAR-T cell team meets with you. The health care team will do some tests to make sure that your health is stable and that you are free of infections. Some people have mild reactions, such as fever, itching, and stomach discomfort, immediately after the infusion. A reaction isn't a sign that the treatment is working or not. Usually, your CAR-T cell team will let you know if you need to stay in the hospital right after the infusion.
Over the next few weeks, CAR-T cells grow and multiply in the body. This can cause inflammatory side effects and affect the brain and nervous system. During this time, your healthcare team keeps a close eye on you and performs daily tests. This can help the healthcare team identify and treat potentially fatal reactions to CAR-T cell therapy early. Depending on how your body reacts to the infusion, you may or may not need to be admitted to the hospital.
When you're not in the hospital, your doctor should stay with you 24 hours a day. Your health care team will tell you what activities you can and cannot do and will impose any dietary restrictions on you. For example, you cannot drive for a long time after the infusion. The results of CAR-T cell therapy can take time.
Ask your healthcare team when you might know how well you're working. During recovery, you are tested for cancer and meet with your specialist to review the results and plan for future care. Once your health is stable, usually about a month after the infusion, you can go home. When you return home, your local healthcare team will take care of your care. Your local care team continues to monitor you for infections and any persistent side effects.
For the first year after CAR-T cell therapy, plan frequent follow-up visits at the hospital where you received the treatment. Continued care may be needed for months or years after CAR-T cell therapy. In addition to follow-up care, consult your primary care team for routine medical care and health problems not related to CAR-T cell therapy. If you have changes in your health or have questions about CAR-T cell therapy, let a member of your CAR-T cell health care team know.
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Chimeric antigen receptor T cell therapy (CAR-T) continues to revolutionize cancer treatment and offers new hope to patients with hematologic malignancies that are difficult to treat. Starting in 2025, seven FDA-approved CAR-T therapies will be available, each targeting specific types of cancer, such as acute lymphoblastic leukemia (ALL), large B-cell lymphoma and multiple myeloma. This review provides an overview of the current development of CAR-T cell therapies for hematological and solid tumors, while examining the challenges associated with their application in AML, ongoing clinical trials, and future directions for optimizing CAR-T cell therapy in the treatment of AML. This review describes that, while no CAR-T treatment has received FDA approval for solid malignancies, certain strategies, such as intracranial CAR therapy aimed at IL-13RA (multifocal glioblastoma) 12 and ongoing clinical trials with claudin18,2 (gastrointestinal tumors12) and GD2 (glioma mutated in H3K27m-125) and neuroblastoma12, are promising. Accordingly, other approaches described in this review that are currently being tested show great potential, such as an autologous T-cell therapy with TCR called afami-cel for synovial sarcoma129 and other cell therapies for HPV-associated cancers.
