CAR T- Cell Therapy

CAR T- Cell Therapy

Chimeric antigen receptor (CAR) T- cell therapy is T cells (a type of white blood cell) which are collected from the patient and transformed in the laboratory to fight against cancer. CAR T- cell therapy is a type of cell-based gene therapy as the genes inside the T cells are altered so they can attack the cancer cells.

CAR T- cell therapy is known as “living drugs”. As the name implies, T cell helps organize the response of the immune system and kill cells that are infected by pathogens, which are known as the backbone of CAR T- cell therapy. Currently available CAR T- cell therapies are customized for each patient.

The treatment process starts with collecting T cells from the patient and re-engineering them in the laboratory to produce proteins called chimeric antigen receptors or CARs that recognize and bind to specific proteins, or antigens, on the surface of cancer cells. After transforming, T cells will be multiplied into millions in the laboratory then delivered back to the patient’s body.

CAR T- cells will continue to multiply in the body and with the instructions from their engineered receptor, they will recognize and destroy cancer cells that exist on the surfaces of the targeted antigens.

Procedures

Collecting T cells

White blood cells including T cells will be removed from the patient’s blood by leukapheresis. This procedure will require patients to lay or sit for 2-3 hours. Two IV lines will be used to withdraw blood and white blood cells separately then the rests of the blood will be delivered back into the body from another channel. Sometimes central venous catheters are required. Patients may feel numbness and tingling sensations or spasm because of low calcium level during leukapheresis. But this can be treated by medication or IV line to balance the level again.

Making CAR T- Cell

Specific chimeric antigen receptor (CAR) will be produced by adding gene after altering T cells in the laboratory. Then these cells will be multiplied into a vast number for treatment to work. Generally it takes several weeks to retrieve certain number of CAR T- cells.

Receiving CAR T- Cell Infusion

After obtaining a certain amount of CAR T- cells, they will be given back to the patient before being multiplied again in the immune system. Before receiving CAR T- cell infusion, chemotherapy will be given to the patient first to reduce the number of other immune cells. This can better activate the CAR T- cells to fight against cancer. The chemotherapy that is given at this stage is not usually too strong as CAR T- cell works best where there are still some cancer cells to destroy. Once CAR T- cells start to bind with the cancer cells, their number increases and they begin to kill more amount of cancer cells.

How CAR T- Cell Therapy Works

The immune system has the responsibility to recognize foreign substances in the body by locating proteins known as antigens. Those antigens are attached on the surface of cancer cells. Immune cells that are known as T cells possess their own proteins known as receptors. Receptors are attached to the foreign antigens and stimulate other parts of the immune system to kill foreign substances. Antigens and immune receptors have a lock-and-key type of relationship. As locks can only be opened with the correct keys, foreign antigen also has a particular immune receptor that can only bind with cancer cells.

Cancer cells have antigens as well, however if the immune cells of the patient don’t have correct receptors, they will not be able to attach to the antigens and kill the cancer cells. Different cancers have different antigens, the treatment requires therapy for each Car T- cell to be specific to each cancer’s antigen. For instance, leukemia or lymphoma cancer cells’ antigen is called CD19. The Car T- cell therapy for this type of cancer will only destroy this cancer cell as it has already recognized, but not other types because no CD19 antigen exist on other cancers.

CAR T- cell therapies account for more than half of all trials for hematological malignancies but these are very helpful in treating some types of cancer, even when other treatments are no longer working.

• Hodgkin’s lymphoma
• CD33, CD123, FLT3 in acute myeloid leukemia
• BCMA in multiple myeloma
• Acute lymphoblastic leukemia (ALL)
• Diffuse large B-cell lymphoma(DLBCL)
• Follicular lymphoma
• Mantle cell lymphoma
• Some autoimmune diseases such as SLE

The initial development of CAR T- cell therapies focused widely on acute lymphoblastic leukemia (ALL), which is the most common type of cancer in children. More than 80% of children are diagnosed with ALL that arises in B cells, the predominant type of pediatric ALL, which can be cured by intensive chemotherapy. But there is a limitation in the application of this treatment in recurrent cancer patients, or relapse after chemotherapy or a stem-cell transplant. Tisagenlecleucel (Kymriah) was approved by FDA and is the first CAR T- cell therapy to treat cancer patients with ALL recurrence. Approximately 60% of cancer children patients are alive more than 5 years and have no chance of cancer recurrence or any relatable diseases after the treatment. CD19-targeted CAR T-cell therapy also offers hope to adults and children with advanced aggressive lymphomas.

CAR T- cell therapy is a very effective treatment for certain cancers that could be challenging to treat. Some side effects may be serious and some may be life-threatening. Thus, the treatment needs to be taken at the hospital where patient can be closely monitored during and after several weeks of receiving this therapy. After CAR T- cells have been multiplied, they release vast amount of chemicals called cytokines, which are known as Cytokine release syndrome (CRS). The side effects can appear as:

• Chills with high fever
• Feeling dizzy or lightheaded
• Difficulty breathing
• Severe nausea, vomiting, and/or diarrhea
• Headaches
• Fast heartbeat and gets tired easily
• Muscle and/or joint pain

After a long-term CAR T- cell therapy, doctors know how to recognize CRS early so they can provide a treatment to control these symptoms as early as possible.

Severe effects on the nervous system such as:

• Headaches
• Confusion or agitation
• Seizures
• Shaking or twitching (tremors) 
• Changes in consciousness
• Unclear speaking and understanding
• Imbalance position

Because of these effects on the nervous system, doctors recommend most of the adult patients not to drive or engage in heavy activities or routine work. Resting for at least several weeks after taking the treatment is advised.

Other possible serious side effects of CAR T- cell therapy may include:

• Allergic reactions during the infusion
• Effect on mineral nutrient level in the body such as low potassium, sodium, or phosphorous.
• Weakened immune, higher chance of getting infection after the treatment.
• Decreased blood cell counts, enhances the risk of infections, fatigue, and bruising or bleeding 

Researchers are relentlessly discovering more data about CAR –T Cell and other cancer treatments. Consulting with the doctors about the symptoms and potential health risks of each patient is required to make proper treatment plan. As Vejthani uses precision medicine approach, every patient is thoroughly investigated for accurate diagnosis before receiving integrated personalized treatment.