CAR T-cell Therapy ▷ Procedure, experience & specialists

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Specialists in CAR T-cell Therapy
Information About the Field of CAR T-cell Therapy

Specialists in CAR T-cell Therapy

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IOZK - Immuno-Oncological Centre Cologne

Immuno-Oncology

Cologne

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Information About the Field of CAR T-cell Therapy

CAR T-cell therapy is a new therapy that can be used for advanced cancers where previous treatments have been unsuccessful. Genetically modified T-cells teach the immune system to recognize cancer cells that it was previously unable to realize. In this way, it can fight tumor cells that it otherwise would not have recognized as such, and previously therapy-resistant tumors can be treated.

What Is CAR T-Cell Therapy?

CAR T-cell therapy is a form of immunotherapy for advanced cancers that have not been successfully treated with previous treatments. T-cells are a subset of white blood cells in the acquired immune system and defend against diseased and defective cells. However, they can only recognize these if an antigen receptor presents the antigens on an endogenous cell. For this reason, in the case of cancer, T-lymphocytes may not identify the cancer cells and consequently destroy them.

CAR stands for chimeric antigen receptor and is a synthetically produced receptor in the laboratory that is incorporated into the genome of the T-cell as genetically modified information. The synthetic protein now appears on the T-cell surface and can subsequently recognize cancer cells present in the body. By recognizing the target structure of the tumor cell, the T-cell is activated and can fight the malignant cells.

The advantage of the CAR-T cell is that it can identify and attack the cancer cells without the presentation by auxiliary molecules. In addition, the new information in the genetically modified cells is retained even after cell division so that daughter cells also carry the new antigen on the cell surface. In this way, the immune system can now fight tumor cells that it would otherwise not have recognized as such, and previously therapy-resistant tumors can also be treated.

How Does CAR T-Cell Therapy Work?

The therapy is carried out using several steps. First, white blood cells are filtered from the patient in a blood draw. This filtering out of white blood cells is also called leukapheresis. In the next step, the T-cells are removed from the remaining white blood cells in the laboratory, where the new genetic information is then inserted into the cell genome. With the help of genetically modified information, the T-cell can now produce the protein that appears on the cell surface and recognizes degenerate cells as an antigen receptor. The modified T-cells are now called CAR-T cells.

To prepare the patients for the return of the modified T-cells, so-called conditioning is carried out. This means that chemotherapy is administered to reduce the patient's remaining T-cell count and make room for the modified T cells. This subsequently facilitates the spread of genetically modified cells. After chemotherapy has been administered, the new CAR-T cells can be placed in the body. This reimplantation is performed via an infusion and takes place under intensive inpatient monitoring.

For Which Diseases Is T-Cell Therapy Used?

Currently, only CAR T-cell therapies targeting the surface antigen CD19 are approved in Germany. This surface protein CD19 is a protein that binds to the surface of B-lymphocytes. For this reason, the therapy can be used to treat primarily B-cell diseases. These diseases include blood and lymph gland diseases, such as leukemias and lymphomas. Also, the state of current research is the treatment of multiple myeloma and lupus erythematosus, an autoimmune disease. However, both diseases are not yet approved for therapy with CAR T-cells.

In general, the therapy is particularly promising for tumors that have a well-defined antigenic property to healthy body tissue.

Procedure and Duration

The course of treatment is gradual and requires several weeks of treatment.

After the patient's T-cells have been collected, they are processed in the laboratory. This procedure can take several weeks and up to one and a half months. Meanwhile, bridging therapy may be given to keep the patient's cancer under control.

Chemotherapy in preparation for reimplantation lasts about three days and requires a subsequent break of a few days. Then, the infusion to return the T-cells can occur, which subsequently involves inpatient monitoring to control possible side effects.

This inpatient stay usually lasts between ten to fourteen days. After discharge from the hospital, patients should maintain close contact with their treatment center, as complications can still occur after fourteen days. For this reason, close follow-up is of high importance.

Experience and Risks

The new form of therapy has so far proved to be very promising. Great treatment successes with longer-term tumor freedom have been achieved in far-advanced cancers.

Nevertheless, CAR-T cell therapy also involves serious risks that the patient should discuss in detail beforehand. Due to the intervention in the immune system, serious side effects can occur. These include cytokine storm, accompanied by fever, fatigue, nausea, cardiovascular problems, and breathing difficulties, so treatment in the intensive care unit may become necessary.

Similarly, neurological complications may occur, such as damage to brain functions, speech disorders, headaches, and confusion. In rare cases, cytokines cross the blood-brain barrier, brain edema, or other neurotoxic consequences cannot be excluded. In the worst case, this can lead to the patient's death. Tumor lysis syndrome, which causes disturbances in kidney function due to the massive death of tumor cells, can also severely affect the patient's condition.

The therapy can cause blood count changes with cell depletion or antibody deficiency and a resulting tendency to infection. This side effect can be treated by antibody administration. In general, intensive monitoring and taking risk-minimizing measures are crucial for the success of the treatment.

Costs and Reimbursement By Health Insurance Companies

The costs for CAR T-cell therapy range between 250,000 and 300,000 euros and are usually covered by statutory health insurance. However, the prices are only covered if the treatment is carried out at a center certified for the therapy. Furthermore, agreements are currently being made between manufacturers and health insurance companies. The insurance companies only have to cover parts of the high treatment costs if the treatment is unsuccessful.

Which Doctors and Clinics Are Specialized in CAR T-Cell Therapy?

CAR T-cell therapy is performed in internal medicine, hematology, and oncology clinics that specialize in treating blood diseases and diseases of the lymphatic system. Therefore, CAR T-cell therapy should only be performed by centers qualified to provide the new treatment.

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