Chimeric Antigen Receptor (CAR) T-cell Therapy in Canada 

Chimeric Antigen Receptor (CAR) T-cell Therapy in Canada or CAR-T therapy is a type of immunotherapy that modifies a patient’s T-cells to better recognize and destroy some types of cancer cells. The human immune system works by identifying all the substances that are original to the individual’s body and keeps track of them. Any foreign substance entering the body then causes activation of the immune cells, causing them to raise an alarm and attack that substance.

T-cells are a type of white blood cells that fight viruses, foreign cells, and cancer cells. CAR-T therapy is aimed at enhancing the effectiveness of T cells. CAR-T therapy uses genetic engineering to alter a patient’s T cells. The genetic material is inserted into the T-cell after it has been penetrated by a type of virus. This then produces transmembrane proteins on the surface of the cell that can recognize specific proteins in the tumour. The particular target for the CAR-T therapy can be chosen during the engineering of the cell itself. Currently, CAR-T therapy against CD19, a marker that is seen in most B cell lymphomas has become the new standard treatment.

Who can benefit from CAR-T therapy?

The therapy is currently used to treat some aggressive subtypes of lymphoma. The physicians will also consider other factors like the age, overall health and fitness of the patient before considering the treatment. The patient’s ability, willingness to travel, and their stamina to withstand the vigorous treatment process will be considered. Based on the information obtained from the clinical trials, there are specific eligibility criteria for each type of CAR-T therapy being considered. But generally, the following types of patients may be considered eligible for the therapy

• The ones that have no significant immune, cardiac or neurological dysfunction
• The ones that have satisfactory organ function and performance status
• Those were diagnosed with the type of cancer that has a CAR-T therapy-approved treatment
• That meets all the regulatory criteria
• That have tumours that express the specific antigen the therapy targets

The doctors will usually discuss the patient’s eligibility and send the relevant medical records to the speciality centre or facility that performs the CAR-T therapy to be evaluated for treatment.

How does the CAR-T cell therapy work?

The process will usually take several weeks to be completed. The process will usually include the following:

T-cell collection  

The white blood cells are removed from the patient using a procedure that is referred to as leukapheresis. The patients are usually in a reclined position for the duration of the removal which is about 3 hours. Two intravenous lines are needed because blood is removed through one line, the white blood cells are separated, and then the blood is returned through another line. A central venous catheter can sometimes be used; it has both IV lines built into it. In some cases, the patient’s blood calcium levels drop, leading to tingling, numbness or muscle spasms. This can be alleviated by replacing the calcium orally or through the IV line.

Engineering of the CAR-T cell 

After the removal of the white blood cells, the T cells are separated and then sent to the lab, where they are altered by adding the gene for the specific chimeric antigen receptor (CAR), which would make them CAR T-cells. These altered cells are then grown and multiplied in the lab. To make the appropriate large number of CAR T-cells that will be needed for the therapy can take several weeks.

Infusion of the altered CAR T-cells 

Once enough CAR T-cells have been made, they are then infused back into the patient. The patient may be administered mild chemotherapy a few days before the infusion. This is to give the CAR T-cell a better chance to get activated to fight the cancer. The chemotherapy is not usually strong enough to leave some active cancer cells that can then be attacked by the CAR T-cell. Once the CAR T-cells start binding with the cancer cells, they immediately begin increasing in number and can help in the destruction of even more cancer cells. 

What are some of the existing CAR T-cell therapies?

CAR T-cell therapies are used in cases when other types of treatment have been tried. They can be employed in some cases of leukaemia, lymphomas, and multiple myelomas. Some examples of currently approved CAR T-cell therapies include:

• Ciltacabtegene autoleucel or cilta-cel (Carvykti)
• Tisagenlecleucel or tisa-cel (Kymriah)
• Brexucabtagene autoleucel or brexu-cel (Tecartus)
• Idecabtagene vicleucel or ide-cel (Abcema)
• Lisocabtagene maraleucel or liso-cel (Breyanzi)
• Axicabtagene ciloleucel or tisa-cel (Yescarta)

A lot of other CAR T-cell therapies are being clinically studied and undergoing trials in the hope that they can be employed in the treatment of other cancer cells as well.

What are the side effects of the therapy?

Several short and long-term side effects are related to the CAR T-cell therapy. The patients are advised to be close to the treatment centers for several weeks after the therapy where they will be closely monitored. Most of the short-term side effects can be managed by supportive therapies, but other side effects can be severe and potentially life-threatening. They may also require treatment in an ICU of the facility or a hospital. Some of the side effects include:

Cytokine Release Syndrome 

As the CAR-T cells are released and multiply inside the patient’s body, their immune system is activated and releases a massive number of inflammatory cytokines into the blood, which causes the syndrome. It can occur within the first few weeks after the infusion or later in some cases. The duration and the intensity can also vary. Some patients will feel only mild flu-like symptoms, while others will have high fevers, hypoxia, multi-organ toxicity and low blood pressure.

Nervous system issues 

The CAR T-cells can affect the patient’s brain, which can lead to various symptoms like agitation, confusion, and a general lack of awareness. The patients may also experience headaches, difficulty with oral or written language, occasional seizures and anxiety. The nervous system issues can occur with or without the cytokine release syndrome. If the patient has experienced CRS, however, neurotoxicity is more common in occurrence. It is reversible in most cases, but in some rare instances, cerebral oedema associated with neurotoxicity may develop, which is potentially fatal.

Macrophage activated syndrome 

This is the severe inflammation of the immune system, which can lead to multi-organ failure.

B cell aplasia 

This is a low number of B cells or even no B cells at all.

Febrile neutropenia 

Neutropenia is the abnormal decrease in the number of certain white blood cells in the blood, usually accompanied by fever.

Hypogammaglobulinemia 

This is a reduction in all types of gamma globulins. It also includes the antibodies that help fight infections. The severe side effects are often a result of the high activity of the immune system, which can be brought on by CAR T-cell therapy. Immunosuppressive drugs and corticosteroids are used in symptom management to stop the side effects while preserving the CAR T-cell. 

The patients and the caregivers must identify the symptoms quickly to initiate the appropriate treatment early enough. This is especially so as the symptoms of some of the side effects are the same as other medical conditions that have alternative treatments.