CAR-T Cell Therapy: Revolutionizing Cancer Treatments Day-By-Day

CAR T. This four-letter acronym represents a treatment that is helping cancer-affected patients. Cancer has a vast impact on those suffering from it, and, with its 90% success rate, Chimeric Antigen Receptor T-cell therapy (CAR T-cell therapy) is there to help them.

What does CAR T-cell therapy even mean and how does it relate to the UN Sustainable Development Goal 3: ‘Good Health and Wellbeing?’ To understand that, we have to learn more about the basis of cancer and other available treatments.

What is the Purpose of CAR T-Cell Therapy?

You have most likely heard about the dangerous disease known as cancer. Research on this mind-boggling disease has been going on for a long time. Believe it or not, developments in cancer treatment started 250 years ago, with new discoveries being made to this day [1]. Researchers are still struggling to fully understand this life-threatening disease because there are many layers to it.

Each year, there are around 10 million deaths due to cancer and around 18 million new cancer cases globally [2]. By 2040, new cancer cases are estimated to increase to around 30 million people worldwide [2]. There is around a 1/3 chance of getting cancer in a person’s lifetime, which is dangerously close to a coin-flip [3].

Even though cancer has a pretty large growing rate, it starts small because it develops from a gene mutation in a single cell. Then, this cell begins to abnormally divide into numerous cells, and the bundles of cells form a solid tumor. The tumors can be malignant (cancerous) or benign (non-cancerous) [4]. Even though it may seem like benign tumors aren’t dangerous because they are non-cancerous, that is not the case. Even though they can't spread through the body, they can still surround or grow towards vital organs; this can hurt the body, especially if they press on major blood vessels or nerves [5]. 

When the word ‘tumor’ comes to mind, people usually think of a solid tumor; however, not all cancers form solid tumors. For example, leukemia does not form a tumor - instead, abnormal white blood cells are produced, decreasing the abundance of healthy blood cells [4]. Other types of cancer, such as breast cancer and liver cancer, do start off with solid tumors. There are over 100 types of cancers; there could be many more that we are yet to discover [4]. CAR T-cell therapy cannot treat all of these forms of cancer, but there could be improvements to help with its versatility in the future. Some cancers that current CAR T-cell therapy can treat are different types of lymphomas, cancer of the lymphatic system (e.g. high-grade B-cell lymphoma), and some forms of leukemia [6].

Different factors, such as smoking, a poor diet, and old age can contribute to your risk of forming cancer. Smoking is one of the main causes for lung cancer, as poisons in cigarettes or vapes can weaken the immune system. Because of this, your body has a lower chance of staying strong against cancer. Having a poor diet also gives rise to this risk - this is a pressing issue in society as many people do not have the resources to get the proper nutrients they need each day. Lastly, as you age, there is more time for your cells to get damaged, and over time they become weaker and more susceptible to complications. With all these factors in mind, treatments are designed to help those who are suffering.

Current Cancer Treatments

Chemotherapy, immunotherapy, radiotherapy... The list goes on and on. There are many different types of cancer treatments currently out there, and they all have their differences and similarities. Unfortunately, none of these treatments work flawlessly, so scientists keep working on improving them. As a result, there are more treatments in the works.

One of them, chemotherapy, is a standard treatment that uses drugs to destroy cancer cells. How does it work? It works by targeting cells that reproduce faster than the average cell [7]. The negative side of this method is that it can target other fast-growing cells (hair cells, skin cells, etc.), which is why patients lose hair during chemotherapy. There are both long-term and short-term effects of this treatment. Long-term effects may include increased risk of a stroke, infections, nerve damage, etc. Short-term effects may include hair loss, insomnia and nausea [8]. 

How does the immunotherapy (more specifically CAR T-cell therapy) process compare to this? Chemotherapy inputs a drug into a body, and the drug does the work. CAR T-cell therapy takes the patient's T-cells (a part of the immune system that focuses on specific foreign particles) and modifies them to attack the cancer cells [9]. Chemotherapy and immunotherapy are quite different, and both of them serve their purpose to various cancers.

Radiotherapy works quite differently compared to both chemotherapy and immunotherapy. As the name implies, radiotherapy works by applying large doses of radiation to the patient in the spot(s) where cancer has formed or spread [7]. Patients under treatment will continuously undergo radiotherapy sessions around five times a week for about three to ten weeks, depending on their situation. Since it can also damage normal cells in the body, radiotherapy has severe side effects such as hearing loss and nausea. People experience these side effects because radiation is very dangerous and if our bodies take high doses of it, there are bound to be different consequences [7]. Compared to CAR T-cell therapy, radiotherapy uses an outside source to work: nothing is injected in or out of the body. 

Treatments like chemotherapy, immunotherapy and radiotherapy all work in their unique ways, and they can provide a lot of benefit to the patient. Still, it is vital to remember that not everything is perfect. The treatment that the patient can get is all based on their state of health and preference, their needs, and the type of cancer in their body. With this in mind, CAR T-cell therapy is available to help patients who need it - and it is time to discover how it really works.

Dissecting CAR T-Cell Therapy

Chimeric antigen receptor T-cell: what do these words actually mean? A chimeric antigen receptor (CAR) is a lab-created receptor designed to attach to specific proteins on cancer cells. Because the receptor is for your unique cells, this cell therapy is a type of personalized treatment. T-cells are an essential part of your immune system as they attack a specific antigen, a substance that causes your immune system to produce antibodies against the cancer cells. The receptor alters the T-cells to combat cancer cells. The patient's T-cells are then given back to them, and cancer can get eliminated [6]. Of course, we have only dipped our toes in the deep end, but now it is time to dive into the details.

Step 1: Collect the blood containing the T-cells from the patient. We cannot magically extract the blood from thin air - instead, we have to use a process called apheresis. Apheresis is a procedure in which the patient's blood is passed through a machine that extracts a certain amount of T-cells from the blood. The blood is then circulated back into the patient: this isn’t life-threatening, but the patient might experience different symptoms (nausea, dizziness, etc.) due to the machine collecting the white blood cells.

Step 2: The T-cells are sent to a laboratory where they are genetically engineered to contain CARs on their surface. This occurs by introducing DNA to the cells, causing the cells to produce CARs which allow the T-cells to recognize the antigen on the targeted cancer cells. 

Step 3: These modified T-cells are then cultured to produce millions of cells in the laboratory. After this time-consuming process is over, the T-cells are frozen and sent back to the patient's hospital or clinic. 

Step 4: Before the infusion, patients may undergo chemotherapy to create space in their immune system for the CAR T-cells to increase in numbers.

Step 5: Soon after chemotherapy is given, the CAR T-cells are infused into the patient using a method similar to blood transfusion [6].

There are periods before treatment where the patient has to be tested to see whether they need CAR T-cell therapy or another type of treatment. Then, after all these steps are complete, the patient will have to recover in the hospital or clinic to make sure nothing goes wrong. 

Afterwards, it is time for the body to take care of things. The CAR T-cells take charge, attaching themselves to cancer cells and destroying them. They continue to do this until there are no cancerous cells left. During this time, some of the cells can divide to create more CAR T-cells, making the process quicker [6].

Studies show CAR T-cell therapy can treat cancer effectively, which is one of the main pros. It is one of the faster treatments available, as all that is needed is a single infusion. The patients do have to wait until their T-cells come back from the lab, but there is usually no need for a second round of treatment after the infusion is over. If you think about it, CAR T-cell therapy is a living drug, and the benefits it gives can last many, many years. Since the CAR T-cells can stay in the body for a lifetime, they can detect and attack new cancer cells in the case of a cancer relapse.

The Side Effects

One of the common side effects of CAR T-cell therapy is cytokine release syndrome (CRS). The syndrome lasts for a very short time, between five to seven days, usually occurring two to four days after the infusion of the CAR T-cells. It is like an extreme version of the flu, with symptoms such as body aches and high fever. CRS occurs because attacking the cancer cells causes an immune response in the body [10]. However, even though there is medication that can help, such as the FDA-approved tocilizumab, the syndrome can still be deadly and cause organ failure.

Another side effect of this treatment is CAR T-cell related encephalopathy syndrome (CRES). Encephalopathy is an overall term for any brain disease that alters the brain function or structure. CRES can cause patients to become confused and may stop them from speaking for a few days. It usually starts around five days after the infusion. However, this side effect can be completely reversible. This syndrome is more common in people who have been treated for lymphoma [11].

Current FDA-Approved T-Cell Therapies

What FDA-approved CAR T-cell therapy treatments are currently available?

ABECMA® is for adult patients with relapsed myeloma. Myeloma occurs when plasma cells become cancerous and have profound effects, such as preventing your body from creating bone cells [12].

BREYANZI® is for adult patients with relapsed or refractory large B-cell lymphoma. This type of lymphoma is a blood cancer in the lymph nodes (located in parts of the body such as the neck, between lungs and around the gut). As the name suggests, this lymphoma affects B-cells.

Much like BREYANZI®,  YESCARTA™ is for patients with certain types of B-cell lymphoma. KYMRIAH™ is part of the same group, but can also provide treatment for young adult patients with relapsed acute lymphoblastic leukemia [12].

TECARTUS™ is for patients with relapsed mantle cell lymphoma. This type of lymphoma can affect the mantle zone in the lymphatic system, which is a system that moves lymph (a fluid) back into the heart [12]. 

It is very likely that more new treatments for cancer will be developed, but there are certainly also going to be enhancements to current treatments such as CAR T-cell therapy.

Future Inventions for Solid Tumors

The future is unpredictable as everything is continuously evolving, and we are adapting to the innovations coming our way. For example, as we know, CAR T-cell therapy cannot work on solid tumors, but there may be a future invention like this that helps in the oncology field.

That being said, what stops CAR T-cell therapy from working on solid tumors? First off, the CAR T-cells have to migrate to the tumors and survive long enough to kill all the tumor cells. The cells surrounding the tumors are often immunosuppressive, which can generate an immune response causing the CAR T-cells to die quicker [13]. Ongoing research shows that adding a molecule from our natural killer cells (large granular lymphocytes) can make CAR T-cells more effective in treating solid tumors. This new generation of CAR T-cell therapy is still in the early clinical stage, but we might see an improvement, and a decrease in cancer deaths, in a couple of years due to the new cancer treatment [14]!

What future treatments can we expect? One of them is personalized treatments. This involves developing a treatment especially for the patient which has their unique features. Cancer mutations are most likely very varied from one patient to another (even if they have the same kind of cancer), so the same treatment could cause different reactions [14]. Personalized treatments could significantly help in cases of cancer that have significant and unique mutations in the gene.

Another opportunity that is being tested is gene editing. Gene editing has been used for many unique reasons, and using it on humans may create a whole different pathway in medicine. More specifically, the gene editing method CRISPR/Cas9 has been used to make modifications to genes that could interfere with the cells’ ability to kill cancer cells [14]. In current trials, scientists are using CRISPR/Cas9 to remove a particular gene in T-cells that tumor cells can manipulate to start gaining entrance.

UN SDG 3 shows that it is important for people to be healthy and safe. This goes hand-in-hand with CAR T-cell therapy as this cancer treatment is aimed at helping to improve the health of people worldwide.

Technology and the medical field are evolving quicker and quicker as we go. With the help of CAR T-cell therapy, many more cancer treatments could be developed and this would change the world for the greater good. Staying informed on the news, whether it is about cancer or any other disease, can help in the long run, and can keep the world on its feet.

References

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[3] J. Cannavo, “What are the Chances of Getting Cancer?,” TruGenX. [Online]. Available: https://trugenx.com/probability-of-getting-cancer/. [Accessed 18 October 2021].

[4] National Cancer Institute, "What Is Cancer," National Cancer Institute, May 5, 2021. [Online]. Available: https://www.cancer.gov/about-cancer/understanding/what-is-cancer. [Accessed 9 June 2021].

[5] A. Stuart, “Benign Tumors,” WebMD, July 25, 2021. [Online]. Available: https://www.webmd.com/a-to-z-guides/benign-tumors-causes-treatments. [Accessed 18 October 2021].

[6] Dana-Farber Cancer Institute, "Frequently Asked Questions About CAR T-Cell Therapy,"  Dana-Farber Cancer Institute, n.d.. [Online]. Available: https://www.dana-farber.org/cellular-therapies-program/car-t-cell-therapy/faq-about-car-t-cell-therapy/. [Accessed 9 June 2021].

[7] National Cancer Institute, "Types of Cancer Treatment," National Cancer Institute, n.d.. [Online]. Available: https://www.cancer.gov/about-cancer/treatment/types. [Accessed 10 June 2021].

[8] The American Cancer Society medical and editorial content team, “Chemotherapy Side Effects,” American Cancer Society, May 1, 2020. [Online]. Available: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/chemotherapy/chemotherapy-side-effects.html. [Accessed 13 August 2021].

[9] National Cancer Institute, “CAR T-cell therapy,” National Cancer Institute, n.d.. [Online]. Available: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/car-t-cell-therapy. [Accessed 14 August 2021].

[10] The American Cancer Society medical and editorial content team, "CAR T-cell Therapy and Its Side Effects," American Cancer Society, April 5, 2021. [Online]. Available: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/car-t-cell1.html. [Accessed 11 June 2021].

[11] D. Carter, "CAR T cell therapy side effects in lymphoma patients," The University of Texas MD Anderson Cancer Center, September 23, 2019.[Online]. Available: https://www.mdanderson.org/cancerwise/car-t-cell-therapy-side-effects-in-lymphoma-patients.h00-159306201.html. [Accessed 11 June 2021].

[12] UPMC Hillman Cancer Center, "FDA-approved CAR T-cell Therapies," UPMC Hillman Cancer Center, September, 2019. [Online]. Available: https://hillman.upmc.com/mario-lemieux-center/treatment/car-t-cell-therapy/fda-approved-therapies. [Accessed 12 June 2021].

[13] Dana-Farber Cancer Institute, “How CAR T-Cell Therapy Works,” Dana-Farber Cancer Institute, n.d.. [Online]. Available: https://www.dana-farber.org/cellular-therapies-program/car-t-cell-therapy/how-car-t-cell-therapy-works/. [Accessed 15 June 2021].

[14] C. R. Fernández, "Four New Technologies That Will Change Cancer Treatment," Labiotech.eu, October 15, 2019. [Online]. Available: https://www.labiotech.eu/in-depth/cancer-treatments-immuno-oncology/. [Accessed 14 June 2021].