An innovative treatment called CAR T-cell therapy uses the body’s immune system to fight cancer. Abbreviated as “Chimeric Antigen Receptor T-cell therapy,” this sort of immunotherapy has transformed the way that some diseases are treated, especially blood cancers like lymphoma and leukaemia.
With CAR T-cell therapy, the immune system is better able to identify and eliminate malignant cells, as compared to standard treatments like chemotherapy and radiation, which target cancer cells while also damaging healthy cells.
In this article, we will explore CAR T-cell therapy, including its process, benefits, and potential side effects.
What Are T-Cells?
Understanding T-cell function is essential for understanding CAR T-cell treatment. White blood cells, known as T-cells, are compulsory to the immune system. They identify malignant or contaminated cells in the body and eliminate them. However, in cancer patients, T-cells often fail to recognise cancer cells as a threat because cancer cells can invent mechanisms to evade the immune system.
CAR T-cell therapy aims to overcome this challenge by modifying the patient’s T-cells so they can specifically target cancer cells. In this procedure, a patient’s T-cells are removed, their genes are changed to produce the chimeric antigen receptor (CAR), and the patient’s body is then reinfused with these improved cells.
The Process of CAR T-Cell Therapy
Here is the step-by-step process of CAR T-cell therapy:
T-Cell Extraction
Collecting the patient’s T-cells through a procedure known as leukapheresis is the initial stage in CAR T-cell treatment. Following the patient’s blood draw, the remaining blood components are recovered to the body, and the T-cells are separated and collected. With little disruption to the patient’s routine, the treatment usually takes a few hours and is performed in a clinic setting.
Genetic Engineering
The extracted T-cells are then genetically modified in a laboratory. Using a viral vector, scientists introduce the gene responsible for creating the chimeric antigen receptor (CAR) into the T-cells. Once the T-cells manifest CAR on their surface, they can specifically target cancer cells. The genetic engineering procedure can take several weeks due to the need to ensure that the CAR T-cells are precisely and properly changed.
Expansion of CAR T-Cells
After genetic modification, the CAR T-cells are cultured and expanded in large numbers to ensure there are enough modified cells to fight cancer once effectively reintroduced into the patient’s body. This expansion process can yield millions of CAR T-cells, which are then tested for quality and potency before being prepared for infusion.
Reinfusion into the Patient
The patient receives a new infusion of CAR T cells after sufficient growth has occurred. An intravenous (IV) infusion is usually used for this. After that, these cells go throughout the body in search of and destroy cancer cells. The reinfusion is generally preceded by a brief course of chemotherapy to reduce the patient’s existing immune cells, making space for the newly modified CAR T-cells.
Post-Treatment Monitoring
After the CAR T-cell infusion, patients are closely monitored for any signs of effectiveness and potential side effects. This monitoring is critical, as CAR T-cell therapy can result in a strong immune response, which may lead to complications. Monitoring typically involves regular blood tests, physical examinations, and imaging studies to track the therapy’s impact and address any side effects early.
Benefits of CAR T-Cell Therapy
The following are the key benefits of CAR T-cell therapy:
1. Long-Term Remission
One of the most significant advantages of CAR T-cell therapy is its potential to prompt long-term remission in patients who have not responded to other forms of treatment. After receiving CAR T-cell therapy, some patients have maintained their cancer-free status for years. This durability offers a life-saving option for those with relapsed or refractory cancers.
2. Personalised Treatment
With CAR T-cell therapy, a patient’s cells are used to produce a customised course of treatment. By using this method, the chance of rejection and other side effects from receiving treatment abroad is reduced. The therapy makes better use of the patient’s biology to deal with the disease by using their immune cells.
3. Precision Targeting of Cancer Cells
CAR T-cell treatment is highly targeted and only targets cancer cells, in contrast to chemotherapy and radiation, which can harm both healthy and malignant cells. It can result in fewer side effects and less damage to healthy tissue. This precision also makes CAR T-cell therapy a powerful option for tumours resistant to conventional therapies.
Side Effects of CAR T-Cell Therapy
While CAR T-cell therapy has shown remarkable potential in treating cancer, it is also connected with a range of side effects. These side effects are primarily due to the immune system’s strong response to the treatment. Below are the most common and significant side effects of CAR T-cell therapy:
1. Cytokine Release Syndrome (CRS)
One of the most frequent and dangerous side effects of CAR T-cell therapy is cytokine release syndrome (CRS). It happens when the immune system is stimulated by the infused CAR T-cells, which causes an overabundance of cytokines to be released. Proteins called cytokines help control the immune system, but when they are produced in high concentrations, they can lead to systemic inflammation.
Symptoms:
- High fever (over 100°F or 38°C)
- Fatigue and malaise
- Low blood pressure (hypotension)
- Rapid heart rate (tachycardia)
- Difficulty breathing (dyspnea)
- Organ dysfunction (e.g., kidney or liver issues)
2. Neurological Toxicity (ICANS)
CAR T-cell therapy’s neurological adverse effects are referred to as immune effector cell-associated neurotoxicity syndrome or ICANS. The exact cause of ICANS is not fully understood, but it is thought to be related to the inflammation triggered by the CAR T-cells.
Symptoms:
- Confusion and disorientation
- Difficulty speaking (aphasia)
- Tremors or seizures
- Headaches
- Loss of coordination or balance
- Reduced alertness or responsiveness
- Severe cases may involve swelling in the brain, which can lead to blackouts or even death.
3. B-Cell Aplasia
CAR T-cell therapy often targets proteins found on the surface of cancerous B-cells, such as CD19, which are also present in healthy B-cells. As a result, CAR T-cells may destroy both cancerous and healthy B-cells, leading to B-cell aplasia, a condition in which the body has very few or no B-cells. A patient with B-cell aplasia may be less able to produce antibodies, making them more vulnerable to infections.
4. Tumour Lysis Syndrome (TLS)
When many cancer cells are quickly destroyed, their contents are released into the bloodstream, and a condition known as tumour lysis syndrome (TLS) is experienced. The rapid discharge of cellular material has the potential to overburden the body’s metabolic functions and result in severe consequences.
Symptoms:
- Nausea and vomiting
- Muscle cramps or spasms
- Irregular heartbeats (arrhythmias)
- Kidney damage or failure due to high levels of uric acid, potassium, and phosphate
5. Infections
CAR T-cell treatment can weaken or suppress the immune system, raising the risk of infection in those receiving it. It can be due to B-cell aplasia, the use of chemotherapy before CAR T-cell infusion, or the effects of the therapy itself on immune function.
Common Infections:
- Bacterial infections (e.g., pneumonia, urinary tract infections)
- Viral infections (e.g., cytomegalovirus, herpes simplex)
- Fungal infections (e.g., candidiasis)
6. Hypogammaglobulinemia
When the blood’s immunoglobulin (antibodies) levels are excessively low, it’s known as hypogammaglobulinemia. Patients may experience hypogammaglobulinemia as a result of CAR T-cell therapy’s potential to reduce B-cells, which are in charge of generating antibodies.
Symptoms:
- Frequent infections
- Weakness and fatigue
7. Blood Cell Depletion
CAR T-cell therapy can also impact various types of blood cells, resulting in conditions such as anaemia, thrombocytopenia, and neutropenia. Anaemia, caused by a lessened red blood cell count, leads to fatigue and shortness of breath. Thrombocytopenia, a reduction in platelet count, heightens the risk of bleeding and bruising. Neutropenia, marked by a low neutrophil count, increases susceptibility to infections, making patients more vulnerable to illness.
Conclusion
In conclusion, CAR T-cell therapy is a significant development in cancer treatment that gives new hope to patients with specific blood cancers. Its distinct ability to precisely target cancer cells and possibly cause long-term remission distinguishes it from conventional treatments. However, there are also significant risks and side effects, especially with respect to immune responses. The possible use of CAR T-cell therapy for managing a greater variety of tumours and enhancing patient outcomes worldwide might increase as research advances.
