By Emmeleia Psyllaki
Our bodies are made up of trillions of cells 1. These cells grow and multiply through the process of cell division to form new cells to meet our body’s needs. Sometimes, however, this process becomes disrupted and stops functioning normally. In that case, abnormal or damaged cells multiply and grow when they are not supposed to. This uncontrollable growth is the disease we all know as ‘cancer’ 1.
These abnormal or damaged cells that are produced can lead to the formation of big lumps of tissue, which we call tumors 1. These can travel and invade nearby tissues as well as more distant places in the body forming new, secondary tumors in a process called metastasis, in this way spreading to other parts of the human body from where it initially started 1. This feature of tumors makes cancer a very dangerous and deadly disease, making it the second cause of death worldwide after cardiovascular disease 2. In 2020 only, it accounted for nearly 10 million deaths, or nearly 1 in 6 deaths 3, hence directly affecting millions of people worldwide, but also their families and friends who suffer their journeys and losses battling this ‘evil demon’ that is cancer.
However, despite it being a leading cause of death worldwide, a cure has not yet been found with many asking, “Can we find a cure for cancer?” “Will we EVER cure cancer?” 4.
Regardless of this lack of hope of actually curing cancer, researchers, scientists and doctors are not anywhere near giving up this race so easily, constantly attempting to discover potential novel treatments. Surgery for the removal of a tumor, chemotherapy, and radiation therapy have been the main ways to target and potentially treat cancer for many years now 5. However, while these continue to be very useful and used on a daily basis, new treatments which can contribute to a change in the treatment landscape for cancer patients are surfacing, such as chimeric antigen receptor (CAR) T-cell therapy 6.
CAR T-cell therapy is the equivalent of “giving patients a living drug,” 5 said Renier J. Brentjens, M.D., Ph.D., of Memorial Sloan Kettering Cancer Center in New York, one of the first leaders in CAR T-cell therapy. As their name reveals, T cells play a vital role in the immune response by protecting our body from infection and in fighting cancer 7 and are key in this process. CAR T-cell therapy involves initially removing T cells from a cancer patient followed by genetic modification in the laboratory to insert a gene that codes for proteins found on their surface, called chimeric antigen receptors, or CARs. In this way, they produce a so-called CAR T-cell. They then grow millions of these CAR T-cells and infuse them into the circulation of the patient where they will expand. Guided by their engineered receptors, they can detect and bind to specific antigens or proteins on the surface of cancer cells, destroying and eventually killing them 5.
Successful treatments for patients whose cancer relapses after being treated with one of the most common cancer treatments, such as chemotherapy, are limited 5. However, CAR-T cell therapy has proven to have long-term effects and survival with no relapse was reported in many patients who received this treatment. More specifically, a clinical trial was performed where children with relapsed ALL were treated with CAR T-cells 5.
Following this clinical trial, 60% of the ALL children who had relapsed survived and were cancer-free after five years 5. So, it was concluded that CAR-T cell therapy could eradicate cancer, especially in patients with relapsed acute lymphoblastic leukemia (ALL). It was also found that this therapy has incredibly successful results in B-cell lymphoma as well 5, hence it is very frequently used for various types of this particular cancer 6.
However, like everything in life and all the other available cancer treatments, despite CAR-T cell therapy’s effectiveness against some very hard-to-treat types of cancer, it does not come without its side effects. One of its most severe side effects is the cytokine release syndrome (CRS). T cells release cytokines which are chemical messengers that direct and stimulate the body’s immune response 5. As CAR-T cells multiply, they produce large amounts of cytokines which they release into the circulation, flooding it. This leads to severe side effects, such as abrupt drops in blood pressure and dangerously high fevers, which can sometimes be fatal 6.
CAR T-cell therapy can also cause immune-effector cell-associated neurotoxicity syndrome (ICANS) which involves problems in the nervous system, such as seizures, confusion and agitation, headaches and trouble with speech and comprehension 6. Unfortunately, the exact cause of ICANS remains elusive at this time and hence requires more research 5.
However, scientists constantly searching for ways to eliminate these severe side effects found a drug and steroids, which can help with CNS and ICANS respectively. The drug tocilizumab (Actemra) initially prescribed to arthritis patients to treat inflammatory circumstances 5, inhibits the function of IL-6, which is a cytokine that T cells and macrophages release in significant numbers 6. In addition to this, steroids, especially dexamethasone, are used for the treatment of ICANS. However, tocilizumab appears to be ineffective with ICANS, despite being extremely effective for treating CRS 5.
In conclusion, despite its side effects, CAR-T cell therapy has provided patients with B-cell lymphoma and ALL with a lot of hope for potential treatment. Hence, further research, study and trials must be performed to fully understand its side effects. This will enable their successful elimination of their severeness as well as increase of the effectiveness of CAR-T cells in treating cancer, as this therapy seems very promising… And hopefully, in a few years’ time, successful CAR-T cell therapy will lead to less lives will be lost due to cancer and less families will be suffering the loss of their loved ones.
References:
- National Cancer Institute. NIH National Cancer Institute. [Online]. Available from: https://www.cancer.gov/about-cancer/understanding/what-is-cancer#:~:text=Cancer%20is%20a%20disease%20in,up%20of%20trillions%20of%20cells. %5BAccessed 19 November 2022].
- Ritchie, H., Spooner, F., Roser, M. Our World in Data. [Online]. Available from: https://ourworldindata.org/causes-of-death %5BAccessed 19 November 2022]
- World health organization. World Health Organization. [Online]. Available from: https://www.who.int/news-room/fact-sheets/detail/cancer [Accessed 19 November 2022].
- Bilby, E. Horizon . [Online]. Available from: https://ec.europa.eu/research-and-innovation/en/horizon-magazine/will-we-ever-cure-cancer#:~:text=Cancer%20is%20a%20group%20of,of%20cases%20than%20currently%20happens. [Accessed 19 November 2022].
- National Cancer Institute. NIH National Cancer Institute. [Online]. Available from: https://www.cancer.gov/about-cancer/treatment/research/car-t-cells [Accessed 20 November 2022].
- American Cancer Society. American Cancer Society. [Online]. Available from: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/car-t-cell1.html [Accessed 20 November 2022].
- Augustyn, A. Brittanica. [Online]. Available from: https://www.britannica.com/science/T-cell %5BAccessed 20 November 2022].
Imperial Bioscience Review 