CAR T-cell therapy is an immunotherapy for cancer. It uses the body's own immune defenses as an ally in the fight against cancer. For CAR T-cell therapy, white blood cells are genetically modified in the laboratory so that they can recognize and specifically destroy cancer cells. CAR T-cell therapy has so far been successfully used to treat various forms of blood cancer.
Overview: What is CAR T-cell therapy?
The weapons of the body’s immune system include T lymphocytes, a subtype of white blood cells. Their main task is to fight off infections. However, one of their tasks is also to recognize and destroy cancer cells. These T cells can be stimulated to perform their task more specifically and efficiently. In CAR T-cell therapy, this is done by modifying T lymphocytes using genetic engineering (the abbreviation CAR stands for “chimeric antigen receptor”). In this process, T lymphocytes are taken from the blood of patients and treated in the laboratory so that they form numerous contact sites (receptors) on their surface. The structure of these artificially created contact sites matches the surface of the tumor cells to be combated like a key to a lock. They are to be used later to dock specifically onto the tumors in order to destroy them. With CAR-T cell therapy, each patient thus receives an individual treatment that is unique in this form. This is because the CAR-T cells that are to fight the cancer originate from the patient’s own body. The natural T-lymphocytes have become “armed” blood cells: the CAR-T cells. These are fed back to patients by infusion to fight the cancer.
CAR T-cell therapy - the procedure
This particular form of immunotherapy for cancer requires several different steps. They extend over several weeks.
First step: Blood is taken from the affected person. It flows into a device that “filters out” and retains the white blood cells; all other components of the blood are returned to the body. This process is called leukapheresis and takes a few hours.
Second step: T cells are separated from the white blood cells.
Third step: In a highly specialized laboratory, genetically engineered features (chimeric antigen receptors – CAR) for the cell surfaces of the T cells are inserted into their genetic information and the cells are multiplied. This process takes several days to weeks. At the end of this process, the desired CAR T cells with tumor-specific contact sites have emerged from the T cells.
Fourth step: Before CAR T cell therapy can begin, the number of blood cancer cells in the patients is reduced and conditions are created in which the CAR T cells given later can multiply. This is achieved with mild chemotherapy called lymphodepletion. It usually lasts for a few days.
Fifth step: The actual CAR T-cell therapy begins with the infusion of the CAR T-cells previously produced in the laboratory. This requires a single infusion, which usually takes less than half an hour. Now the CAR-T cells can take effect in the body by continuing to multiply, docking with the tumor cells and destroying them.
Sixth step: The patient remains in the hospital for about 10 to 14 days for monitoring
Types of cancer: When is CAR T-cell therapy used?
CAR T-cell therapy has been approved in Switzerland and other European countries since October 2018. To date, it has been used for the following malignant blood diseases:
Leukemia (blood cancer) in the form of B-cell acute lymphoblastic leukemia (medical abbreviation: B-ALL).
Lymphoma (cancer of the lymph glands) in the form of diffuse large B-cell lymphoma (DLBCL) or primary mediastinal large B-cell lymphoma (PMBCL).
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CAR T-cell therapy: advantages and risks
Previous studies with CAR T-cell therapy have shown that the treatments often bring the desired success. The tumor burden can be significantly reduced in many patients. Patients can even be completely tumor-free and cured by the treatment. The CAR-T cells do not have to be removed from the patient’s body after treatment. They remain there and could even become active again later if tumors form again. The following side effects may occur: Cytokine release syndrome (CRS) is the most common side effect of CAR-T cell therapy, usually occurring within the first 14 days after the start of therapy. In this case, there is a massive accumulation of cytokines in the blood, as a result of an overreaction of the immune system or as a concomitant of the decay of tumor cells. CRS symptoms include:
Fever
Fatigue
Circulatory problems
Vomiting
Cramps
Confusion
If CRS occurs, those affected are monitored as inpatients. Medication can help to alleviate or eliminate the side effects. Neurological side effects also occur. Nervous system disorders occur, for example, in the following form:
Headache
Dizziness
Sleep disturbances
Problems finding words; the person affected recognizes an object, for example, but cannot name it.
These side effects, which usually disappear within a week, can also be alleviated. Changes in blood values are also likely as a side effect of CAR T-cell therapy. Not only B cells affected by cancer, but also healthy B cells are recognized by the CAR-T cells – and combated. Similarly, non-specific suppression of healthy blood formation in the bone marrow may occur. This results in an increased risk of infections for those affected. This can be mitigated by inpatient monitoring in hospital. Antibody deficiency can be a further problem in the long term, as these are produced by mature healthy B cells, which are also attacked by the CAR T cells. Antibodies are an important part of the immune system. they are missing, the risk of infections increases. Their deficiency can be treated by injecting the body with antibodies from outside.
CAR T-cell therapy: What does the future hold?
Scientists are working intensively to develop CAR-T cell therapy for other types of cancer. One problem that has not yet been solved is that while CAR-T cells can reach diseased blood cells relatively quickly, this is more difficult with solidly growing tumors. To reach them and destroy them, the CAR-T cells need more time. However, this is limited: Only direct contact with the surface of the tumor causes the CAR-T cells to proliferate. Another problem is that solid tumors often do not show attack structures on the surface that are sufficiently different from healthy tissue. Thus, there is a risk that the healthy organs are also attacked, which can lead to severe side effects.
