One advantage of chimeric antigen receptor (CAR) T-cell therapy is that it is administered in a single infusion and therefore requires shorter treatment time. Other advantages of CAR T-cell therapy include the following:
- Boosts the immune system
- Improves immunogenic memory, which provides continuous surveillance to treat local and distant metastatic lesions
- Recognizes and eliminates damaged cells and cells infected with harmful pathogens, such as viruses and cancerous cells
- Reduces the need for aggressive chemotherapy
- May replace the need for transplants
- May prevent or cure cancer relapse after transplant surgeries
Even though cancer cells have different origins and complexities, they share common target antigens, such as CD19, CD20, CD22, and many more, which allow CAR T cells to detect tumor cells regardless of cell origin.
What is CAR T therapy?
CAR T-cell therapy is a type of targeted therapy that may be effective in treating certain cancers. This treatment method is an experimental form of gene therapy that trains T lymphocytes—immune cells that attack abnormal, damaged, infected cells—to more efficiently kill cancer cells.
With CAR T-cell therapy, blood is drawn from your body, cells in the blood are separated and manipulated, and then the blood is injected back into your body:
- Leukapheresis, or the isolation of your peripheral blood, is the first stage of this therapy.
- Apheresis is a technique that is commonly used to isolate blood and split it into its components.
- The isolated T cells are then genetically changed before being reinjected into your body. These T cells are more potent than regular T cells present in the body and have shown better cancer-fighting abilities.
Currently, blood banks use apheresis to collect platelets and other blood components for the treatment of a variety of illnesses, including hematologic and renal problems. As a result, it is viewed as a risk-free technique for healthy patients.
What are the limitations of CAR T therapy?
Although CAR T-cell therapy has emerged as a potential cancer treatment, challenges include the following:
- Long-term follow-up in clinical trials is necessary for improved persistence and cytotoxic profile of CAR T-cell therapy because:
- Effectiveness is dependent on cancer cells expressing unique antigens, an atypical character of aggressive cancers
- Some of these antigens will cause unwanted side effects
- CAR T-cell therapy has been linked to several serious side effects, including:
- Neurological toxicity (damage to the brain and nervous system)
- Cytokine release syndrome (CRS) (acute inflammation in the body indicated by fever or multiple organ dysfunction)
- B cell aplasia (reduced B type immune cells)
- Tumor lysis syndrome (multiple tumor cells die and release their contents into the blood, which is harmful to the body)
- Allergic reaction
- The multiplication of CAR T cells in the body creates cytokines that can kill cancer cells.
- Symptoms of CRS-associated toxicity range from mild to severe and may include:
- Another unintended consequence is the presence of CAR T cells that target antigens on the surface of the B or T cells, which are both cancer and normal cells, leading to B cell aplasia. As a result, a detailed examination is required to assess the qualities of B cell aplasia.
- Similarly, tumor lysis syndrome can cause toxicity due to the collapse of dead cells in the early stages of cancer treatment. It may potentially cause organ damage and endanger the patient's life.
- CAR T-cell therapy is less effective against solid tumors because solid tumors are surrounded by an immunosuppressive microenvironment that dampens the immune system.
How effective is CAR T therapy in cancer treatment?
CAR T-cell therapies that target cancer cells expressing the surface antigen CD19 have proven extremely effective in treating some blood cancers, such as B cell acute lymphoblastic leukemia.
The therapy has also proven to be moderately scalable and not prohibitively expensive. This has encouraged the testing of CAR T-cell treatment techniques for various tumors using a wide range of tumor antigens and strategies to manufacture highly sensitive chimeric receptors.
According to clinical trial reports as of 2016, there have been 150 CAR T cell clinical trials for solid tumors and 131 CAR T cell clinical trials for blood cancers such as leukemia, lymphoma, and myeloma.
However, CAR T-cell therapy has not been very successful in the treatment of solid (nonhematologic) tumors.
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National Institutes of Health. CAR T-cell therapy. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/car-t-cell-therapy
Cleveland Clinic. CAR T-Cell Therapy. https://my.clevelandclinic.org/health/treatments/17726-car-t-cell-therapy
Brodsky AN. The Promise of CAR T Cell Therapy in 2019 and Beyond. Cancer Research Institute. https://www.cancerresearch.org/en-us/blog/september-2019/promise-car-t-cell-therapy-2019-beyond
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