What Is CAR T Cell Therapy?

In today's world, many diseases are evolving quickly and becoming harder to treat. The healthcare field is moving into an era of personalised treatments, tailored for each patient and their disease. One such personalised treatment is CAR T-cell therapy, a specialised therapy for cancer that uses  one’s own immune cells. 

Read on to learn more about CAR T-cell therapy and its process, the different types of cancer it can treat, how it is beneficial, and what can be  expected in terms of recovery if one undergoes CAR T-cell therapy. 

Overview

Chimeric antigen receptor T-cell therapy, commonly known as CAR T-cell therapy, is a type of cancer immunotherapy treatment that uses  the patient’s immune cells to attack cancer cells. The immune system is closely connected to cancer development, as cancer cells need to evade the immune system’s ability to eradicate them in order to keep developing and dividing. Our immune system has many cells: one  such important cell type is T cells (a type of white blood cell) which protect us against bacteria, viruses, toxins and even cancer.^1,2

In CAR T-cell therapy, T cells from a patient’s blood are collected and transformed genetically into cancer-fighting T cells, which can locate and eliminate cancer cells. Given that CAR T-cell therapy involves changing the genes of T cells to enable them to fight cancer, it is considered a form of cell-based gene therapy.^2,3

 Healthy T- cells contain receptors that attach themselves to proteins on the surface of pathogens and cancerous cells called antigens. The attachment of a T-cell receptor to an antigen can be compared to how a key opens a lock.  Each type of cancer cell has a unique antigen on the surface, which can only be recognised by specialised receptors on T-cells. As a receptor and its corresponding antigen bind, a reaction is triggered that causes the T-cell to destroy the cell it is bound to. 

To trigger T-cells to recognise and kill different cancer cell types, scientists created artificial receptors (referred to as chimeric antigen receptors or CAR) and attached them to the T-cell surface to form CAR T-cells. This receptor allows the CAR T-cells to recognise and attach to a specific antigen on the surface of cancer cells and effectively destroy them.^1,2

Given that the T-cells used are extracted directly from the patient and each CAR  corresponds to a specific type of cancer antigen, this treatment is extremely personalised for each patient, and no two patients receive  the same type of therapy. 

What is the process of CAR T-cell therapy?

The process of CAR T-cell therapy usually takes a few weeks as it is carefully curated for each individual. It starts with the collection of T cells from the patient, and only after several weeks, patients receive the modified white blood cells.³   

The general steps involved in CAR T-cell therapy are:^1,2,3,4

• Collection of white blood cells: The therapy starts with a procedure called leukapheresis, in which a patient's blood is drawn into a machine that separates white blood cells, red blood cells and plasma. Your doctor will insert two IV (intravenous lines) catheters into a large vein near the neck, chest or arm. One IV line collects the blood, while the other sends back the blood without the white cells into your body. This process takes around 2-3 hours

Leukapheresis can occasionally result in a decline in blood calcium levels, which is normalised using IV or oral (tablets) calcium.

• Making of CAR T-cells: After the collection of white blood cells from the patient, T cells are separated and sent to the laboratory. Scientists add the specific chimeric antigen receptor (CAR) genes to the T-cells, making them CAR T-cells. Once enough CAR T-cells are  produced, they are tested against the particular cancer type. This process takes several weeks. Once it passes the tests, these cells are ready for patient use

• Conditioning of a patient’s immune system: During the CAR T-cell production process, the patient's body is prepared to receive the therapy. Chemotherapy or other therapies may be used to weaken the patient's immune system so that their body allows the multiplication of CAR T-cells. This process requires hospitalisation in most cases, as constant monitoring is needed to ensure the patient’s overall health is protected

• Infusion of CAR T-cells: The patient receives the CAR-T cells through IV infusions over a few hours. Once the CAR T-cells enter your bloodstream, they reach the cancer cells and attach to their antigens. Over time the CAR T-cells multiply and eliminate the cancer cells

• Monitoring after therapy: After receiving CAR-T cell therapy, patients will be monitored closely for a few weeks to make sure the therapy is functioning as expected and to manage any potential side effects. The post-treatment hospitalisation could last up to 10 days or more, depending on the patient’s recovery rate

Talk with your doctor/oncologist before the start of therapy to understand its duration and potential side effects. The therapy process is long and could be exhausting on your physical and mental health, so you’ll need to take time to rest and recover with the help of your healthcare team, family and friends. 

What cancers are treated with CAR T-cell therapy?

The US Food and Drug Administration (FDA) has given the green light for CAR T-cell treatments to treat certain leukaemias, lymphomas, and multiple myeloma cases. In the event that all other cancer treatments fail, CAR T-cell therapy is administered.³  

In the UK, the NHS is providing NICE-approved CAR T-cell therapy for blood cancers such as:^4,5,6

• B cell acute lymphoblastic leukaemia: Eligible patients are children and young adults up to 25 years old

• Diffuse large B-cell lymphoma: It is approved for adults who have received two or more previous treatments that failed in eradicating this type of cancer

• Primary mediastinal B-cell lymphoma:  CAR T-cell therapy is approved in adults who have relapsed (got the same type of cancer again) or have not responded to previous treatments

Currently, only certain blood cancers are treated with CAR T-cell therapy. There are, however, ongoing clinical trials and research to explore the use of CAR T-cell therapy in other types of cancer (solid tumours) such as lung, breast, or brain cancer.

Advantages of CAR T-cell therapy

CAR T-cell therapy has proven advantageous in effectively treating certain types of blood cancers.

Some of the advantages are: ^3,7,8

• Personalised therapy: CAR T-cell therapy is a type of targeted therapy which is  personalised for each patient. The use of the patient's own T-cells to create the therapy increases its effectiveness

• Promising results in treating blood cancers:  Patients with leukaemias, lymphomas, and multiple myeloma have shown a decrease in the number of cancer cells after receiving treatment to the point of complete cancer eradication

• Effective and long-lasting: CAR T-cell therapy is highly effective in treating patients who have not responded to other treatments. Furthermore, it provides long-lasting results - some patients who underwent the therapy remained cancer-free for several years

• Non-invasive: CAR T-cell therapy does not require surgery or radiation as it is delivered directly into the bloodstream. This treatment is a one-time therapy; therefore, there is no need for repeated sessions

Disadvantages of CAR T-cell therapy

Although CAR T-cell therapy is an advanced and effective treatment strategy, more studies are  required to fully understand the side effects it can cause and ways to prevent these.

Some disadvantages surrounding CAR T-cell therapy are:^3,7,8

• Extreme side effects: Frequent side effects of CAR T-cell treatment include fever, nausea, vomiting, and neurological problems. These side effects can occasionally be severe or even life-threatening

• Can only treat a few types of cancer: Currently, the therapy can only treat a few types of blood cancer, and there are many regulations surrounding its administration to patients

• Limited effectiveness: While CAR T-cell treatment has shown excellent results in many cases, it might not be helpful for patients with other types of cancer. Some individuals may not respond to treatment and end up having a recurrence of the cancer

• Expensive and limited availability: CAR T-cell therapy is a relatively new, complex, and pricey medical procedure. Through the NHS, the therapy is fairly accessible, but at the same time, there is limited access due to how expensive it is for the NHS to administer this therapy to patients

Side effects of CAR T-cell therapy

CAR T-cell therapy is very effective in treating certain cancers, but it can occasionally have terrible or even fatal side effects. Due to this, it must be administered at a hospital with staff that has received specialised training, and patients must be constantly monitored for several weeks after receiving the CAR T-cells.

Some primary side effects observed are:^3,4,5,8

• Cytokine release syndrome (CRS): A major side effect of CAR T-cell treatment is CRS, which can result in fever, low blood pressure, a fast pulse, and breathing problems. It is a systemic inflammatory and immunological response that is triggered as the CAR T-cells get activated and release small proteins called cytokines into the bloodstream. There are ongoing studies on how to detect and treat CRS earlier

• Neurological issues: Neurological side effects of this therapy include disorientation, seizures, headaches, shaking/twitching and trouble speaking or interpreting speech. These symptoms might range from moderate to severe, and can persist for a few days

• Blood Disorders: Some individuals can develop anaemia, as CAR T-cell therapy can lower blood cell count. Some patients also experience abnormal blood mineral concentrations, such as low potassium, sodium, or phosphorous levels, as a result of the therapy

• Infections: Patients may become more susceptible to infections as a result of the therapy's effects on the immune system. In the first few weeks following therapy, patients must be careful when going out or interacting with others

• Tumour Lysis Syndrome (TLS): This is an uncommon yet severe adverse effect that can happen when a lot of cancer cells are rapidly killed. TLS may lead to adverse effects such as renal damage, irregular heartbeats, and other complications

• Allergic Reaction: Some individuals have also had an allergic reaction to the CAR T-cells when they were infused

It is important to discuss the potential side effects with your doctor before treatment, and to monitor for any signs and symptoms that may ensue after treatment. If you experience any of the symptoms mentioned above, make sure to go to A&E to receive immediate medical attention. 

How long does it take to recover from CAR T-cell therapy?

Depending on the patient and the degree of side effects they experience, recovery times might vary. While some individuals may recover faster, others might need hospitalisation and a lengthier recovery time. The recovery period could range between 2-3 months. CAR T-cell treatment may result in serious or fatal adverse effects. Because of this, doctors typically advise patients to stay in the hospital for a few days so they can watch for and treat any side effects.^5,8

You should prepare to have someone with you constantly to help with chores, driving to and from the hospital, and for moral support for the first month following therapy as it is a critical recovery period. 

Summary

CAR T-cell therapy is a personalised cancer immunotherapy which uses genetically modified T-cells to selectively target and eliminate cancer cells. T-cells from a patient's blood are genetically altered to become cancer-fighting through the insertion of CAR genes. As every CAR is designed for a specific tumour antigen, the therapy is highly personalised. Phases of the CAR T-cell therapy process include white blood cell collection, CAR T-cell generation in a lab, immune system conditioning of the patient, CAR T-cell injection, and post-treatment monitoring.

Around the world, the therapy is approved for the treatment of a few types of blood cancer. In the UK, it is approved for treating B-cell acute lymphoblastic leukaemia, diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma. 

There are many advantages and disadvantages of this therapy. The major disadvantage is the severe side effects that patients can experience, such as cytokine release syndrome (CRS), neurological issues and more. Hence, after receiving CAR T-cell treatment, patients require close monitoring and management by a healthcare team over the course of several weeks until they’re fully recovered.