By Angel Maria Siji, 22nd May 2023
BRIEF HISTORY
At the mere age of six years old, Emily Whitehead was diagnosed with acute lymphoblastic leukaemia, now claimed to be the most common “childhood cancer”. Ten years ago, Tom and Kari Whitehead, parents of this little girl, came to the Children’s Hospital of Philadelphia (CHOP) looking for a miracle. After months of unsuccessful chemotherapy against a disease that progressed at a life-threatening speed, Emily was eventually deemed unfit for a bone marrow transplant to treat leukaemia. Family and friends were notified that there was nothing left to do, except to allow her to pass away in peace.
Unwilling to lose all hope, parents Tom and Kari enrolled their daughter in a newly-founded immunotherapy treatment - so recent that it was never tested on a child before. Together with established and determined researchers around the globe, Dr Stephan Grupp, a pioneer in the field of cell immunotherapy devised a new treatment and coined it the CAR-T cell therapy. By using one’s immune system against the disease, Dr Grupp introduced this therapy that reengineered the patient’s T-cells to attack cancer cells. What followed was an intense year, full of trips to the hospitals, filled with anticipation, fear and the slightest ray of hope. And in June 2012, at the age of 7, Emily Whitehead was discharged from the hospital after successfully battling leukaemia. Thus began the journey of a life-changing treatment that has saved thousands of lives ever since the FDA approved the therapy in 2017.
What is CAR-T cell therapy?
CAR-T cell therapy or Chimeric antigen receptor uses immune cells called T-cells (a type of white blood cell) to fight cancerous cells after being modified externally under laboratory conditions. It involves altering genes present inside these immune cells to locate, target and eventually destroy cancer cells.
Typically, one’s immune system recognizes foreign substances in the body by finding proteins called antigens on the surface of said foreign bodies. T-cells come with receptors that attach to antigens and trigger an immune response to eradicate the foreign substance. The relationship between antigens and immune receptors is like that of a lock and its key. Just as each lock has its key, each antigen has its specific receptor.
Cancerous cells also have antigens, but if your immune system is incapable of producing the right receptors, the antigens can’t be identified and destroyed.
Fig. 1. Brueggeman, Mauri. “CAR-T Cells Attacking Cancer Cells .” CAR-T Cell Therapy 101, 14 Dec. 2018, https://www.labroots.com/trending/cancer/8617/car-t-cell-101. Accessed 18 Apr. 2023.
Process
Firstly, white blood cells are separated from the patient’s blood via leukapheresis. This involves IV lines being inserted to draw out the blood. WBCs are then removed and the rest of the blood is returned to the bloodstream.
Next, the T-cells are isolated and sent to the lab for modification. This involves the addition of a gene for the specific chimeric antigen receptor (CAR). The cells, now called CAR-T cells, are cultured for several weeks to make the necessary amount required for this therapy.
Soon, the cells are infused into the patient’s bloodstream.
A few days before the CAR-T infusion, the patient may undergo a few rounds of chemotherapy to lower their immune cell count. This gives the CAR-T cells a better chance at fighting cancer. Once the binding of the receptors with their antigens begins, the T-cells increase in number and can help destroy even more cancerous cells.
Fig. 2. Hucks, George, and Susan R. Rheingold . The Journey to CAR T Cell Therapy, 22 Jan. 2019, https://www.nature.com/articles/s41408-018-0164-6. Accessed 18 Apr. 2023.
Side-effects
Although this therapy was seen to be very effective against malicious forms of cancer, it could bring about a few serious side effects. Thus, it is of the utmost importance that the therapy is administered at a credible and established medical centre and by medical professionals. Patients also need to be closely monitored for several weeks after the CAR-T cell infusion.
Furthermore, an increased number of CAR-T cells releases large amounts of chemicals called cytokines. This could lead to a disorder called cytokine release syndrome (CRS). Side effects include:
· Fever and chills
· Breathing issues
· Nausea, vomiting and diarrhoea
· Dizziness or lightheadedness
· Muscle and/or joint pain
Every human body is unique in its own way and may react differently to the therapy. Some may experience severe allergic reactions and others may have a weakened immune system, which puts them at increased risk of serious infections and illnesses. It is very important to report any side effects to your healthcare right away, as there often are medicines to treat them.
Works Cited
American Society of Clinical Oncology (ASCO). ASCO Annual Meeting 2019: Immunotherapy for lung cancer, gastrointestinal cancers and targeted therapy for breast cancer. Accessed at https://www.cancer.net/blog/2019-06/asco-annual-meeting-2019-immunotherapy-lung-cancer-gastrointestinal-cancers-and-targeted-therapy on December 19, 2019.
American Society of Clinical Oncology (ASCO). Understanding immunotherapy. Accessed at https://www.cancer.net/navigating-cancer-care/how-cancer-treated/immunotherapy-and-vaccines/understanding-immunotherapy on December 19, 2019.
Bayer VR, Davis ME, Gordan RA, et al. Immunotherapy. In Olsen MM, LeFebvre KB, Brassil KJ, eds. Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice. Pittsburgh, PA: Oncology Nursing Society; 2019:149-189.
National Cancer Institute (NCI). (NCI). CAR T cells: Engineering patients’ immune cells to treat their cancers. Accessed at https://www.cancer.gov/about-cancer/treatment/research/car-t-cells on December 19, 2019.
Porter DL, Maloney DG. Cytokine release syndrome (CRS). UpToDate. 2021. Accessed at https://www.uptodate.com/contents/cytokine-release-syndrome-crs on April 01, 2021.
Brueggeman, Mauri. “CAR-T Cells Attacking Cancer Cells .” CAR-T Cell Therapy 101, 14 Dec. 2018, https://www.labroots.com/trending/cancer/8617/car-t-cell-101. Accessed 18 Apr. 2023.
Hucks, George, and Susan R. Rheingold . The Journey to CAR T Cell Therapy, 22 Jan. 2019, https://www.nature.com/articles/s41408-018-0164-6. Accessed 18 Apr. 2023.
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