Treating Cancer with CAR T-Cell Immunotherapy

By: Derek Martinez


Cancer is one of the most prominent diseases in the world, it being the 2nd highest leading cause of death in the United States as ranked by the CDC. One factor for this unfortunate statistic is that it is also one of the hardest diseases to treat due to its nature. Cancer is caused by a human’s own cells, making anti-pathogenic treatments ineffective. Normally, our cells grow and divide when new cells are needed, and dead cells are replaced with new cells. With cancer however, damaged and old cells survive when they are meant to die, and new cells are formed when they are not necessary. The excess new cells can divide indefinitely and cause the formation of growths called tumors.


One common treatment to kill these fast-growing cells is chemotherapy, but this has severe side effects for a patient and can cause them to feel very weak. One innovative solution to this is a treatment called CAR T-Cell Immunotherapy. Before delving into how this treatment works, it could be beneficial to see where the term comes from. Immunotherapy is a combination of the terms immuno and therapy. Immuno refers to the immune system, and therapy is a treatment. So immunotherapy is a treatment that is meant to boost a patient’s immune system, in this case to fight cancer. CAR is an acronym that stands for “Chimeric Antigen Receptor.” Chimeric refers to a creature from Greek mythology called a “Chimera,” which is a hybrid animal mixed with a lion, a goat, and a snake. The reason why the receptor is described as chimeric is because the receptor is a “hybrid” between antigen-binding and T-cell activating functions. Antigen refers to a molecular structure found on the surface of pathogens. Antibodies are able to bind to antigens and flag them for the immune system to destroy. So in a sense, antigens are like ID cards which can be recognized by antibodies. Receptor refers to the structure that is engineered onto the surface of T-cells, which we will get into later. Lastly, T-cells are a type of white blood cell that works within the immune system. There are two major subtypes of T-cells: killer and helper. Killer cells are able to directly target and kill virus-infected cells, while helper cells help in the maturation of other cells within the immune system. In short, CAR T-Cell Immunotherapy is just a treatment that engineers immune cells to have a hybrid response to cancer cells.


Methodology

Now onto the specifics. T-Cells are unable to destroy cancer cells since they are not invasive organisms, and thus do not need to be flagged by antibodies. This is a huge obstacle, since the immune system is the most powerful tool that can be used to destroy cancer cells. To get around this, researchers developed a technique in which specific receptors can be added to the surfaces of T-Cells in order to destroy cancer cells through the immune system. A Chimeric Antigen Receptor, or CAR, is added to T-Cells. It functions like an antibody that flags cancer cells, which then allows the T-Cells to identify and destroy them.


Engineering the T-Cells to express the CAR is a multistep and nuanced process. These are the steps researchers will typically take for the therapy:

  1. A blood sample is taken from the patient. In order to isolate just the T-Cells, a process called ficoll separation is done to separate the three components of blood, that being red blood cells, white blood cells, and plasma. The steps of the process are...

  • Adding ficoll, a chemical that separates blood components by density, to the bottom of a tube. The blood sample is layered on top of it.

  • Spinning the tube at a high speed in a device called a centrifuge, which divides the components of a liquid.

  • After the centrifuge is done, the blood sample is now divided into 4 parts, including a layer of ficoll. The layers in order from bottom to top are the red blood cells, ficoll, white blood cells (labeled “buffy coat”), and plasma. The plasma is removed as waste, and the white blood cells are removed from the tube and put into a separate sample.

  • A substance called “PBS” is added to the new sample, which prevents the shriveling or rupturing of cells due to osmosis. The sample is spun in a centrifuge once more.

  • After the centrifuge is done, the sample will be split in two layers of white blood cells and PBS from bottom to top respectively. The PBS is removed, while being sure that the white blood cells are not disrupted. Then, the white blood cells are removed.

2. After the cells are collected, a protein is added to the T-Cells which allows them to

express the CAR receptor on their surface.


3. The newly edited T-Cells are multiplied significantly, essentially creating an army of

CAR T-Cells to fight against the cancer in the patient’s body.


4. After there is a substantial amount of new T-Cells, they are infused back into the

patient’s body. The patient may be given chemotherapy in order to lower the amount of

other immune cells to allow the T-Cells to thrive better.


5. Once in the patient’s body, the T-Cells begin to recognize and destroy cancer cells,

and gradually grow in number.


Though the process is extremely tedious and can take several weeks to complete, previous trials of CAR T-Cell Immunotherapy have been successful and have shown positive results. In one specific study involving lymphoma, 82% of patients were positively affected by the treatment 28 days after it was given. Dr. Michael Bishop, MD, at the University of Chicago has also found that there is a 30-40% success rate of lasting remission with no additional treatment with CAR T-Cell Immunotherapy. This shows promise for the treatment of cancer, and also the future for public health, particularly in the United States.


Image Credit: Pixabay @ DarkoStojanovic


Educational Content:

Q: What differentiates cancer cells from normal cells?

A: Normal cells have an orderly cycle where old and damaged cells die off and are replaced by new cells. This makes it so there is not an excess amount of cells within the body but also not a lack of cells. Cancer cells on the other hand are disorganized and have no control. Old and damaged cells which normally die actually survive, and cells divide when it is not needed. This causes an excess of cells, leading to the formation of tumors.


Q: Why is CAR T-Cell Immunotherapy a better alternative to chemotherapy?

A: Chemotherapy is effective against destroying cancer cells, but patients will have severe side effects from the treatment. CAR T-Cell immunotherapy is much more effective since it uses the body’s most powerful tool to directly destroy cancer cells, and has less side effects. It has also been shown that the treatment has long term positive effects for remission.


Sources:

https://www.cancer.gov/about-cancer/understanding/what-is-cancer

https://www.cdc.gov/healthreport/publications/compendium.pdf

https://www.cdc.gov/hpv/parents/vaccine.html

https://www.uchicagomedicine.org/forefront/cancer-articles/a-walking-miracle-car-t-cell-therapy

https://www.mayoclinic.org/tests-procedures/chemotherapy/about/pac-20385033

https://www.froedtert.com/stories/clinical-trial-shows-more-half-lymphoma-patients-still-remission-six-months-after-treatment


Image Citation:

https://pixabay.com/photos/laboratory-test-tubes-563423/


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