CAR T cell therapy is considered a milestone in personalized medicine and especially in the treatment of cancers such as malignant lymphoma, acute leukemia and multiple myeloma. The innovative therapy uses the body's own T cells from a patient's blood. T cells, also called T lymphocytes, are white blood cells. Their main task is to detect and combat infections. They also play an important role in maintaining immunological balance.
The patient's T cells are genetically modified in the laboratory so that they carry special receptors, so-called chimeric antigen receptors (CARs), on their surface. These receptors allow T cells to recognize and attack certain proteins on the surfaces of cancer cells. After modification, the CAR-T cells are multiplied in the laboratory and returned to the patient via infusion. This allows the body to specifically attack and destroy cancer cells.
Advantage over conventional forms of therapy
“The importance of CAR T-cell therapy currently lies primarily in its effectiveness in the treatment of certain types of malignant blood diseases, such as B-cell leukemias and B-cell lymphomas and multiple myeloma, for which traditional treatments often do not are sufficiently effective,” explains Prof. Dr. med. Claudia Dorothea Baldus, Director of the Clinic for Internal Medicine, Hematology and Oncology at the Schleswig-Holstein University Hospital in Kiel.
The chairwoman of the German Society for Hematology and Medical Oncology eV says: “For certain types of cancer, this relatively new form of therapy has already proven to be effective and safe. This means that it is used earlier and earlier in the treatment.” This pioneering therapy has a clear advantage over conventional treatments such as chemotherapy or radiation: once applied, the modified T cells can act as a “living drug” in the body and ensure long-term immune monitoring.
Cells active for months or years
However, how long these modified cells remain active varies from patient to patient and depends on many factors – the clinical picture, the type of cancer and the patient's individual response to the therapy. Some studies show that CAR T cells remain active for months and even years in some patients.
These successes are possible with certain types of blood cancer – for example, with acute lymphocytic leukemia and with certain forms of non-Hodgkin's lymphoma. “However, this long-term activity is not necessary for all cancers,” says Baldus. “In some cases, short-lived CAR-T cell surveillance and a strong immune response are probably sufficient to destroy the cancer cells.”
Patient numbers are increasing
However, this complex and expensive CAR T-cell therapy also entails risks such as so-called “cytokine storms”, also known as cytokine release syndrome or CRS. A cytokine storm occurs when CAR T cells activated by therapy release a large amount of cytokines. This is a group of protein molecules that are responsible for communication between cells in the immune system. This massive release of cytokines can lead to severe inflammatory reactions with symptoms such as fever, nausea, headaches, general weakness, low blood pressure and, in severe cases, even organ failure.
Monitoring and management of CRS is therefore an important part of implementing CAR T-cell therapy. The aim is to detect these reactions early, treat them in a timely manner and control them. Figures prove the advance of innovative cellular immunotherapy. The first CAR T cell therapy took place in Germany in 2019. In 2022, around 655 treatments were carried out in Germany, and in 2023 around 1,000 patients benefited.
“Today, immunotherapy has arrived in the specialized centers and thus – figuratively speaking – the carpet has been rolled out for broader use in the future,” says the Kiel hematologist and oncologist. “However, the therapy still has a lot of room for improvement. The more specific proteins we identify, the broader the range of individual treatments can become.”
Reduction of side effects
There are currently two proteins in focus – CD19 and BCMA. Both proteins are found on the surface of B cells in many malignant blood diseases. By creating CAR-T products that bind to these proteins, one can specifically direct the patient's immune system to recognize and destroy these cancer cells. CD19 is used as a target structure in acute lymphoblastic leukemia or B-cell lymphomas. BCMA stands for “B-cell maturation antigen” and plays an important role in the treatment of multiple myeloma.
CAR-T cell products targeting BCMA have emerged as a promising treatment option. Specific molecules such as CD19 and BCMA allow CAR T-cell therapy to be highly targeted, resulting in greater treatment effectiveness and potentially a reduction in side effects.
High costs should soon fall
We cannot yet estimate what opportunities the new form of treatment offers in conjunction with conventional therapies such as chemotherapy and radiation therapy or surgical interventions,” explains Baldus. In her opinion, the next few years will be exciting: “Research in this area is very active. Studies are ongoing that concern the effectiveness of this form of therapy for solid tumors. The more experience we have, the better we will be able to assess and control the immune reactions.”
The future will also bring positive results on the cost side. CAR T-cell therapies are still patient-specific, meaning they are time-consuming and cost-intensive. A treatment can cost up to around 350,000 euros per patient. Innovations in manufacturing technology and logistics may soon bring costs down.
So-called off-the-shelf products, also known as “allogeneic” or “universal” CAR-T cells, are also a research goal. This refers to large quantities of pre-produced CAR-T cells that are made from the cells of healthy donors. The advantage is obvious – off-the-shelf CAR-T cells would be immediately available when needed. In the future, standardized treatments may also be able to be developed from prefabricated cells.
