CAR-T therapy has proven to show good results in a range of patients both young and old. This type of immunotherapy teaches T cells to recognize and destroy cancer much more reliably. In some patients, this leads to the total elimination of cancer. There is also a significant amelioration of the disease in others.
What You Need to Know About CAR-T Therapy
The Cancer Treatment Problem
Cancer is a silent killer. Too often, it has devastating results because the cells in the human body are not adept enough at killing it. This is the case with T cells, human immune cells whose responsibility is to fight invasion and disease. These cells, also known as T lymphocytes – a special type of white blood cell – are not as good at recognizing cancer as they should be, leaving humans at the mercy of cancer. The solution? CAR-T cell therapy.
As the Cancer Treatment Centers of America points to CAR-T treatment as a novel way to treat cancer, it could drastically alter the outlook for both children and adults. Otherwise, they would be without the possibility of a cure.
However, they also point out that CAR-T immunotherapy is not a cure-all for every patient. For some, it only works for a short time before the crushing relapse. Other patients respond to it, but suffer such severe side effects that it basically does nothing to ease the symptoms. While researchers work furiously to determine why some treatments work on cancer cells and others do not, they still have not arrived at a firm answer.
That is not to say there is no hope, however; there absolutely is. For those who are facing cancer, either personally or at the side of a loved one, it’s important to answer the question “What is CAR-T?” Therefore, this guide will answer the most common questions about CAR-T cell therapy for readers who want to make the best possible choices for themselves or loved ones.
What Is CAR-T Cell Therapy?
CAR-T cell is pronounced phonetically, as “car tee cell.” CAR stands for chimeric antigen receptor. Named for a mythical creature, the chimera, an animal made of different parts of different animals attached together, CAR-T cells have additional antigen receptors on their surfaces.
First, a brief history of immunology may prove helpful. An antigen is a foreign substance in the body, either a toxin or disease agent or unhealthy cell (as in cancer), that triggers an immune response. The body then produces white blood cells to attack the agent. It does this by binding to it with the use of antigen receptors on the surface of the white blood cells, or lymphocytes. Only then does the body produce antibodies to destroy the foreign or diseased agent.
The problem is T cells, the white blood cells responsible for destroying tumor cells, are not good enough at recognizing it. Therefore, in order to increase the patient immune levels, medical specialists take blood. From the blood, they harvest T cells and add extra antigen receptors to the surface of the cells. They inject those cells back into the patient via blood transfusion, where they multiply and can then attack cancer, either with or without the aid of additional therapies.
Specifically, the antigens can then recognize the protein CD-19, which forms on the surface of B cells, a type of blood cell that frequently becomes cancerous. By knowing which proteins to look for, the modified T cells can hunt them down, attack, and destroy them throughout the bloodstream.
CAR-T Cell Therapy Advancements
Currently, numerous companies are working to perfect the technology of CAR-T cells. Think Akron Biotech, for example, which modifies many types of cells for use in medical treatments. Novartis is another company producing Kymriah, the drug used to treat acute lymphoblastic leukemia. In many ways, Novartis CAR-T is one of the most common right now.
This is a new technology. Not only is it expensive to manufacture antigens in a lab and attach them to T cells, it takes a long time and carries a number of different specifications in order for candidates to gain approval for the treatment. So exactly which candidates can receive therapy?
Who Is a Good Candidate for CAR-T Cell Therapy?
In 2017, the Food and Drug Administration approved the use of two CAR-T cell immunology treatments. During clinical trials and since then, CAR-T therapy has proven considerably effective at treating two types of blood-borne cancer. These include:
- Kymriah: This treatment helps patients 25 and younger, especially children, who have acute lymphoblastic leukemia. It is also effective in adult patients with relapsed non-Hodgkin’s lymphoma, or versions that do not respond to other types of treatment.
- Yescarta: This also treats non-Hodgkin’s lymphoma that has not shown improvement in other types of treatment.
Both treatment protocols modify T cells to help them recognize and attack diseased B cells in the blood. Patients with either leukemia or B-cell lymphoma may apply for the clinical trial at this time. However, they cannot do so without first trying at least two other cancer therapies of a more standard nature.
Currently, researchers are experimenting with CAR-T therapies for other types of cancers as well. These include leukemia and lymphoma subtypes, as well as non-blood-borne cancers. Its ability to fight solid tumors, or those that do not spread throughout blood or bone marrow, have thus far proven less than impressive.
How Does CAR-T Therapy Work?
Physicians make CAR-T cells via a careful process. First, the patient is set up in the hospital and prepped for a blood draw, followed by a long stay. Most patients are quite ill by the time they start CAR-T cell immunotherapy, necessitating they remain in the hospital until the completion of the treatment.
Doctors then take a patient’s blood and feed it into an apheresis machine. This device separates out the white blood cells, T cells included. Then it feeds the remaining blood back to the patient. This means they do not lose a lot of blood while physicians now have a healthy supply of cells to transform. Doctors then freeze the harvested cells and send them off to a lab.
Lab workers then take the collected T cells and introduce a gene that manufactures the chimeric antigen receptor into the DNA of each cell. Lab workers then grow millions of versions of these cells. Once they have enough, they harvest the cells, freeze them once more and deliver them back to the patient via transfusion.
Both these T cells, plus the ones subsequently manufactured by the patient’s body, can then bind to and attack the cancer cells.
What Is CAR-T Treatment Like for the Patient?
Because transforming T cells is such a complex process, the treatment is typically a long one for the patient. From beginning to end, the transformation and reintroduction of cells may take up to 3 weeks. During that time, the patient is compromised even more than usual due to the reduction in their T cell population. That’s why they usually stay in the hospital during the entire process. This way, doctors can monitor them and make sure their immunity stays as robust as possible.
Before introducing the modified T cells to the patient, physicians typically give them a round of chemotherapy. This helps to weaken their immune system further, which reduces the chances that existing T cells will outnumber the new ones. Counterintuitively, by depressing the immune system in the short run, doctors give patients the best chance of engineered T cells multiplying and doing their job.
The transfusion itself is typically short and painless, lasting only about an hour. After staying in the hospital for monitoring, patients must come in regularly for a few weeks afterward.
What Are the Benefits of CAR-T Cell Therapy?
The huge benefit of a treatment like this is the T cell modifications will last for life. Each time a body’s T cells encounter a toxin or disease agent and develop antigen receptors and antibodies to fight it, the person has that ability forever. That means patients who receive modified T cells now have the tools to fight their particular cancer for the remainder of their days.
This makes CAR-T cell therapy more than a treatment. For example, while chemotherapy and radiation are effective, their curative effects end when the treatment ends (or, more accurately, a few days or weeks after the last course). In contrast, modified T cells hang around forever, turning this type of immunotherapy into a “living drug.”
Are There Any Drawbacks of This Treatment?
However, while the drug is long-lasting and may, therefore, prove more affordable than it initially looks, it is an expensive process. Moreover, possible side effects do exist. These include:
- Low blood cell counts
- Shaking and chills
- Vomiting and diarrhea
- Cytokine release syndrome (CRS), in which cytokines (immune system substances) release in large quantities and begin attacking healthy tissue
Plus, while the process is very beneficial to some patients, it is extremely time-consuming. Some question where it can actually serve a broader population, considering the necessary time and specialization required.
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