Mohamad-Ali Salloum is a Pharmacist and science writer. He loves simplifying science to the general public and healthcare students through words and illustrations. When he's not working, you can usually find him in the gym, reading a book, or learning a new skill.
CAR T-Cell Therapy: What do you need to know about it?
Mohamad Ali Salloum, PharmD • Jun 30, 2022
Share
Briefly speaking, it is the use of one’s immune cells- specifically the T-cells- then teach them how to detect cancer cells in our bodies and kill them. It sounds simple, but talking about how to do it, here comes the challenge.
Is this technique approved by FDA?
Is it efficacious? And why is it important to develop?
How did the scientists isolate the T-Cells?
Can it kill both solid and liquid tumors?
How do they teach these cells to detect cancer cells?
How do they allow the cells to proliferate and then inject them back into our bodies in the effort of reducing the complications (e.g., Cytokine Release Syndrome (CRS))?
A LOT OF QUESTIONS can arise, but this technique was not developed in a single night. It was developed over decades and its complexity increases with the more we know. In this article, I am going to talk about the key points that will make you knowledgeable about this technique.
Is this method FDA approved?
Since 2017, Six CAR-T-cell-based therapies were approved by the FDA (1):
- Axicabtagene ciloleucel, approved on 30 August 2017.
- Tisagenlecleucel, approved on 01 May 2018.
- Brexucabtagene autoleucel
- Lisocabtagene maraleucel
- Idecabtagene vicleucel
- Ciltacabtagene autoleucel
After the conduction of several Phase I and Phase II clinical trials, these medications were approved by FDA for the treatment of the below hematological malignancies:
Why is this method significant?
What empowers this method is its ability to treat patients with relapsed and refractory diseases where previous treatments were not enough to eliminate cancer.
As we know, more than 80% of children diagnosed with Acute Lymphoblastic Leukemia (ALL) that arises in B-cells will be cured by intensive chemotherapy. But limited effective treatments are available for those whose cancers return after initial treatment (1). Providing effective treatment with CAR T-cell therapy for these cases is such a blessing!
What is its efficacy?
Large Phase I/II clinical trials at several centers confirmed the high level of efficacy of CAR T cells, particularly in Acute Lymphoblastic Leukemia where complete remission (CR) (the disappearance of all signs of cancer) rates of 70 to 93% are achieved. (2)
How do they work?
White blood cells called T cells are taken from the patient's blood and are modified in the lab by adding a gene for a receptor (called a Chimeric Antigen Receptor or CAR), which helps the T cells attach to a specific cancer cell antigen. The CAR T-cells are then given back to the patient where they will detect the cancer cells and help in eliminating them. I will explain in more scientific detail how they work in a future article.
What are the side effects?
Like all medications, this type of therapy will also cause some side effects, and sometimes these side effects may be life-threatening.
1) Cytokine release syndrome (CRS):
It is the most common one and may lead to serious adverse events. This happens because when CAR T-cells multiply, they will release large amounts of cytokines into the blood and this will hyperactivate the immune system and will lead to (3):
- High fever and chills
- Trouble breathing
- Severe nausea, vomiting, and/or diarrhea
- Feeling dizzy or lightheaded
- Headaches
- Fast heartbeat
- Feeling very tired
- Muscle and/or joint pain
2) Nervous System problems:
- Headaches
- Changes in consciousness
- Confusion or agitation
- Seizures
- Shaking or twitching (tremors)
- Trouble speaking and understanding
- Loss of balance
3) Allergic reactions during the infusion
4) Abnormal levels of minerals in the blood, such as low potassium, sodium, or phosphorous levels
5) A weakened immune system, with an increased risk of serious infections
6) Low blood cell counts, which can increase the risk of infections, fatigue, and bruising or bleeding
Are the side effects manageable?
An article was published in January 2021 discussing the most recent management notes for minimizing adverse effects of CAR T-cell therapy, and they are:
- Continuous close monitoring of the patients,
- Rapid detection of the side effect occurrence,
- Accurate intervention with supportive care, anti-cytokine or corticosteroid therapy.
Thus, prophylactic and/or preventive strategies to avoid toxicities without affecting efficacy and predictors of toxicities should be identified in later studies. (4)
What is the downside of this therapy?
Although a lot of promises are built on this therapy, however, in a study on patients with diffuse large B-cell lymphoma, the scientists observed long-term survival in less than half of the patients treated and that in select clinical scenarios alternate therapies (standard treatment) may be as efficacious as CAR T therapy. Not to mention their extremely high cost, where the most recently approved CAR T-Cell treatment is worth ~450,000$. Thus, more randomized and prospective clinical trials should be conducted to have more clear results. (2) (5)
Can this therapy be used in solid tumors?
CAR T-cell therapy can be effectively used in blood tumors since, for example, in B-cell cancers there are antigens homogeneously expressed (e.g., CD19) on the surface of the cancer cells, and the therapy will be able to identify the cancer cells easily and eliminate them.
Unfortunately, in solid tumors (e.g., lung, prostate, breast cancers…) there is no homogenous expression of antigens on the surface of the cancer cells, and thus the CAR T-Cell therapy will not be able to differentiate between the normal and cancer cells which will lead to its failure as a treatment. (2)
The scientists had an idea and thought that if there is no homogeneity of antigens, then they can target several antigens at the same time. This can be used to prevent the cancer cells from escaping the re-programmed T-cells (6). Another method was developed in a pre-clinical model where CAR T cells secrete IL-12 and lead to the activation of macrophages that mediated the elimination of antigen-negative tumor cells. (7)
A review was done in December 2021 about the current clinical trials using CAR T-cell therapy in solid tumors and they concluded that an extensive amount of ongoing research will be necessary to assess the safety and feasibility of their place in treatment in solid tumors and maybe the success of the ongoing Phase I clinical trials will lead to the conduction of Phase II and Phase III studies in the future. (8)
List of Services
ABOUT THE AUTHOR
Mohamad-Ali Salloum, PharmD
Share
Recent articles:
The story of ultrasound exploration is one of invention and perseverance, driven by an attempt to discover the secrets of the human body. Researchers have pushed the boundaries of science to explore the potential of sound waves for medical imaging, from the creation of sonar technology during World War I and II through the pioneering work of Karl Dussik in Austria. This road of discovery has resulted in a revolution in medical practice, with ultrasound now being used to diagnose and treat a wide range of diseases. Join us on a fascinating tour through the history of ultrasound to see how this extraordinary technology has changed the appearance of modern medicine. To begin, understanding how ultrasound works will help us appreciate the incredible power and promise of this remarkable technology. So, to begin, consider the following question: What is the procedure of an ultrasound?
These strong rays have been used by doctors and scientists for almost a century to gaze into the mysteries of the human body and beyond. But did you know that X-rays were found entirely by chance ? In 1895, Wilhelm Conrad Roentgen, a German physicist, was experimenting with cathode rays (aka electric currents) when he noticed an unusual glow coming from a nearby screen. He had no idea that this unintentional discovery would forever revolutionize the world of medicine! Radiation such as X-rays can travel through the body. They are invisible to the naked eye and cannot be felt. The energy from X-rays is absorbed in varying rates by different regions of the body as they move through the body. After the X-rays have passed through, a detector on the other side of the body collects them and converts them into an image. Dense portions of your body, such as bone, that X-rays find difficult to get through, appear as distinct white patches in the image. Softer tissues that X-rays can easily pass through, such as your heart and lungs, seem darker. So, what’s the true purpose of X-rays? They are commonly used for a variety of evaluations, of which we shall highlight a few: Dental X-rays are used in dentistry to obtain images of the teeth and surrounding tissues, which aid in the diagnosis of oral health concerns and treatment planning. Cancer Treatment: a type of radiation therapy that uses high doses of radiation to eliminate cancer cells in specific parts of the body. Veterinary Care: utilized in veterinary medicine to diagnose and treat animals, assisting veterinarians in the detection of fractures, cancers, and other health problems. Industrial inspection is used to inspect machinery and infrastructure in the industrial sector, assisting in the detection of flaws and the prevention of accidents. Forensic Science: a branch of forensic science that examines the evidence and reconstructs crime scenes to assist in identifying victims of crimes and accidents. Bone Density Testing: used to assess bone density and aid in the diagnosis of osteoporosis and other bone-related diseases. The chart below provides additional information about the medical applications of X-rays:
I’ve always thought that our energy is limited (due to the physical laws of thermodynamics, where it states that energy is neither created nor destroyed, it’s only transformed) and that when we work around 10 hectic hours a day, there’s nothing to do more than go home, eat, watch some tiktoks/reels, and then sleep. I know that our bodies and minds can feel depleted after long periods of exertion, but this feeling is not always an indicator that we are out of energy. Little by little, I am now convinced with the contrary to this theory. It’s not that our energy is finite, but what we can really do is to refresh ourselves to access the energy in us that we always had but never used. Imagine your energy is 100%/day. All your life, you thought that you were using 90-95% of your energy by going to school and then studying after-school, or during the collage days, or even when you started working. The most hectic phase is the work phase, where you are now stuck in adulthood and you have no escape. But this phase will be the best one if you knew how to play it. You are actually using only 50% of your true energy. (ps: I made up this percentage… but let me explain) Now as I am writing this article, I was work-travelling, I woke up today at 4 am, worked on some urgent tasks before going to the hospital, went to the hospital at 8 am and then worked till 6:30 pm. Then I went to the hotel, took a 1-hour rest. And now I am eating lunch and writing this article. When I reached the hotel, I was tired as f**k. I just wanted to take a shower and then sleep, but then I remembered something that always motivated me. (I heard David Goggins talk about it in a Podcast) Imagine when you die, the angels at the gates go through a list of your traits and qualities that you had during your lifetime, and they mention a top tier qualities that you’ve never imagined you will ever have or even mention accomplishments you’ve never thought that you would achieve something near to them. You tell them that they are describing someone else, and this person is not you. They reply to you that this person is the one you would have been if you worked enough on yourself. CHILLS. Imagine not being able to be the best version of yourself, just because you didn’t choose to…you always have the choice, but somehow you find an excuse to not do anything to make yourself better. Or even convince yourself that sending some emails or doing some tasks during the work day is enough to make you excel or reach this version of yourself. So i got up, feeling a whole new energy in me (although I didn’t sleep). I went outside of the hotel to the nearest restaurant, and now i’m finishing this article. After that I will continue working on my Running V-log project that I am currently working on. Step by Step. But the most important thing is to know that you will reach what you want one day if you make enough effort to accomplish it and make less excuses to run from it. The key takeaway is that while our physical energy might have limits, our mental and emotional energy can be optimized through various strategies. By adopting a proactive approach to energy management and changing your perspective of how you see things, you can unlock your full potential and achieve greater productivity and fulfillment.
Adjustment shock is what we feel when life throws us a curveball, causing both our minds and bodies to react. In today’s ever-changing world, this is something we all face. On the flip side, there’s the idea of anti-fragility, a term coined by Nassim Nicholas Taleb. It describes systems that don’t just survive stress but actually thrive because of it. Let’s dive into how our brains can be anti-fragile.
Are you feeling that you are not fulfilled with your life?
The U.S. Food and Drug Administration (FDA) plays a crucial role in ensuring the safety and efficacy of medications. Despite rigorous testing, some drugs are recalled post-approval due to unforeseen adverse effects. This essay explores ten such medications, detailing the reasons behind their recalls.
Couch to 5K :D Let's Do it!
Runner Beginner's Guide: What you need to take into consideration?
Perfectionism, often perceived as a virtue, can paradoxically hinder personal growth and well-being. By understanding the pitfalls of perfectionism, individuals can cultivate healthier mindsets and behaviors.
Introduction Setting realistic running goals is crucial for both beginners and seasoned runners. Goals provide direction, motivation, and a sense of accomplishment. However, setting goals that are too ambitious can lead to frustration and injury, while goals that are too easy may not provide enough challenge. This essay explores the science behind setting realistic running goals, delving into molecular insights and using analogies to make the concepts more accessible. The Science of Goal Setting At the core of goal setting is the brain’s reward system, primarily driven by the neurotransmitter dopamine. When you set a goal, your brain releases dopamine, which creates a feeling of pleasure and motivation. This is why setting and achieving goals feels rewarding. However, the key is to set goals that are challenging yet achievable to maintain a steady release of dopamine and keep motivation high . Molecular Insights On a molecular level, setting and achieving goals involves complex biochemical processes. When you set a running goal, your brain’s neurons communicate through synapses, releasing neurotransmitters like dopamine and serotonin. These chemicals help regulate mood, motivation, and focus. For instance, dopamine is often referred to as the “feel-good” neurotransmitter because it plays a significant role in reward-motivated behavior. Moreover, regular physical activity, such as running, increases the production of brain-derived neurotrophic factor (BDNF), a protein that supports the growth and survival of neurons. BDNF is crucial for learning and memory, which means that setting and achieving running goals can enhance cognitive function and overall brain health . Setting Realistic Running Goals 1.Know Your Starting Point : Assess your current fitness level. This can be done through a simple test, like running a mile and recording your time. Knowing where you start helps in setting achievable goals. 2. Use the SMART Criteria : Goals should be Specific, Measurable, Achievable, Relevant, and Time-bound. For example, instead of saying “I want to run faster,” set a goal like "I want to improve my 5K time by 2 minutes in the next 3 months" . 3.Break It Down : Large goals can be overwhelming. Break them into smaller, manageable milestones. For instance, if your goal is to run a marathon, start with a 5K, then a 10K, and gradually increase your distance. 4.Monitor Progress : Keep track of your progress through a running app or journal. This helps in staying accountable and making necessary adjustments to your training plan. Setting running goals is like building a house. You need a solid foundation (your current fitness level), a clear blueprint (your SMART goals), and regular maintenance (consistent training and progress monitoring). Conclusion Setting realistic running goals is a blend of art and science. By understanding the molecular processes involved and using practical strategies, you can set goals that are both challenging and achievable. Remember, the journey is just as important as the destination. Celebrate each milestone and enjoy the process of becoming a better runner.