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Breaking Down CAR-T Cell Therapy and Its Applications

What are CAR-T Cells?

CAR-T cells are altered versions of typical T cells, which are a type of white blood cell associated with the immune system. Being a crucial part of the immune system, T cells are responsible for recognizing foreign pathogens by molecules expressed on their cell surfaces called antigens. The recognition of a pathogen by a T cell, or other immune cells, typically causes the body's immune system to activate and launch an immune response.


A regular T cell can be taken and genetically edited to express a chimeric antigen receptor or a CAR. CARs are not naturally occurring receptors and have been edited in such a way that they can bind to antigens on cancer cells, which are often capable of evading normal immune cell responses. [1, 2]


How it Works

Effective CAR-T cell treatment occurs in the following:

  1. T cells are removed from the patient's blood using specialized equipment.

  2. A new gene coding for a CAR protein will be added to the collected T cells. Cells that have successfully taken up this gene will express a CAR protein on their cell surface.

  3. After successful CAR-T cells are created, they are allowed to continue growing and multiplying until there is a large number of them available (in the millions).

  4. Once enough modified T cells are available for use, they are infused back into the individual.

  5. Finally, the CAR-T cells reintroduced to the patient's body can bind to and destroy the target cancer cells.

At the moment, CAR-T cells are created for each unique patient, which causes this whole process to take many weeks to be fully complete. [3]


Who is CAR-T Cell Therapy For?

Typically, CAR-T cell therapy has been used as a treatment for individuals with different types of blood cancer. It has been used primarily to treat B-cell acute lymphoblastic leukemia (or ALL) in both children and adults whose cancers have either relapsed or are not responding to other treatments, such as chemotherapy. Other types of blood cancers such as diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), and mantle cell lymphoma (MCL) can be treated with CAR-T cell therapy. [3, 4]


Side Effects of Treatment

CAR-T cell therapy has been associated with some notable side effects that can be organized into two conditions, the first of which is cytokine release syndrome (CRS). This syndrome results from an increase in cytokine release by T-cells within the body. Cytokines are chemicals that are released by T-cells in normal conditions to initiate a response from the immune system to combat infection. It is associated with various symptoms, including intense fevers, fatigue, muscle or joint pain, rapid heartbeat, low blood pressure, headaches or lightheadedness, and difficulty breathing.


CRS can range in severity, from mild to severe to occasionally fatal. However, it is an expected side effect that proves that the immunotherapy is effective as it shows the reintroduced T-cells are properly functioning. Fortunately, milder cases of CRS are easily treated by supportive methods such as steroids, and treatment for more severe cases is actively being researched.


The second condition is called immune effector cell-associated neurotoxicity syndrome (ICANS), which describes the negative neurologic side effects of CAR-T cell therapy. Prominent symptoms include confusion, headaches, hallucinations, difficulty talking or understanding, impaired balance, and tremors or seizures. ICANS, like CRS, can range in severity. Steroids are currently the most effective method to treat ICANS, but research is currently ongoing to find other effective treatment options.


In addition to these conditions, other symptoms to be aware of include vital minerals being unusually high or low in the blood; increased risk of infections, bruising, or bleeding; and allergic reactions. [2, 3, 4]


Current Applications & Potential

Presently, CAR-T cell therapy is primarily used as an immunotherapy for different leukemias. Currently approved treatments are made to recognize two specific antigens on cancerous cells, those antigens being CD19 and BCMA. However, research and clinical trials are currently ongoing to expand the number of approved target antigens that can be recognized by CAR-T cells. There is also hope to utilize CAR-T therapy to treat solid tumor cancers after the challenges such as diverse tumor genetics and identifiable cancer-specific antigens, among others, are overcome.


In addition to this, CAR-T cell therapy will hopefully become more accessible in the future. As it stands, this immunotherapy is often used as a last attempt to treat aggressive leukemia. However, in recent clinical trials, CAR-T cell therapy was observed to be more effective than standard chemotherapy treatment for patients with relapsed non-Hodgkin lymphoma. There are also efforts to make this treatment more accessible by creating so-called "off-the-shelf" therapies. This is done to create a more readily available source of T-cells obtained from healthy donors, which would decrease the amount of time it takes to start the patient's treatment. [3]


References

  1. Car T cell therapy. Memorial Sloan Kettering Cancer Center. (n.d.). https://www.mskcc.org/cancer-care/diagnosis-treatment/cancer-treatments/immunotherapy/car-cell-therapy

  2. Penn Medicine. (n.d.). Car T cell therapy. Pennmedicine.org. https://www.pennmedicine.org/cancer/navigating-cancer-care/treatment-types/immunotherapy/what-is-car-t-therapy

  3. National Cancer Institute. (2022, March 10). Car T cells: Engineering immune cells to treat cancer. Cancer.gov. https://www.cancer.gov/about-cancer/treatment/research/car-t-cells

  4. Cancer Research UK. (2024, July 2). Car T-cell therapy. https://www.cancerresearchuk.org/about-cancer/treatment/immunotherapy/types/CAR-T-cell-therapy


Assessed and Endorsed by the MedReport Medical Review Board

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