CAR T-Cell Therapy: What it is and how it works

08 April,2024

Cellular immunotherapies are the new age cancer treatment. With advances in medical technologies, researchers are constantly improving the scenario of cancer management. CAR T-cell therapy is the latest addition to it. The US FDA approved CAR T-cell therapy for cancer patients in 2017. India's first CAR T-cell therapy was administered on June 4, 2021, at Tata Memorial Center, Mumbai. 

If you are also fascinated by the news of this innovative cancer treatment and want to know more about it, you have landed at the right place. This blog aims to provide all the relevant information about CAR T-cell therapy, including the procedure, cost, and related side effects.

What is CAR T-Cell Therapy?

The primary treatments for most cancers are surgery, chemotherapy, and radiotherapy. Since the 2000s, cancer treatment has shifted from traditional approaches to more personalized ones using targeted and immunotherapy. 

CAR T-cell therapy is an immunotherapy that strengthens the body's immune system to spot and attack cancer cells. T-cells and B-cells are the main lymphocytes that fight off invaders in our body. T-cells do it by identifying specific proteins (antigens) present on the surface of foreign cells. T-cells have receptors that bind to these antigens and destroy them. 

CAR T-cell therapy involves modifying and reengineering T cells in specially designed labs to enhance their capacity to find and destroy cancer cells. It has the advantage of staying active in the body for a prolonged period. Hence, it is a one-time therapy that reduces cancer recurrence chances. 

Which Type of Cancers can CAR T-Cell Therapy Treat?

CAR T-cell therapy focuses primarily on treating leukemia and lymphomas. It benefits people with previous treatment failures, including bone marrow or stem cell transplants. Patients experiencing recurrence of leukemia and lymphoma are also candidates for CAR T-cell therapy.  

The following types of cancers have shown promising results when treated with CAR T-cell therapy – 

• B-cell acute lymphoblastic leukemia (ALL)
• High-grade B-cell lymphoma
• Diffuse large B-cell lymphoma
• Follicular lymphoma
• Mantle cell lymphoma
• Primary mediastinal large B-cell lymphoma

Multiple myeloma is a recent addition to the approved diseases for CAR T-cell therapy. 

What are the Contraindications for CAR T-Cell Therapy?

CAR T-cell therapy is not advisable for everyone. Only specific tumors can be treated using this treatment. Solid tumors do not have a single protein that the CAR T-cells can target. Hence, CAR T-cell therapy is effective against solid tumors of the lungs, breasts, etc. Other contraindications for the therapy may include:

• Severe Organ Dysfunction: Patients having severe organ failure or dysfunction are not suitable candidates.
• Ongoing Infections: Active infections might increase the risk of complications, so patients are first treated for the infection.
• Certain Neurological Conditions: Pre-existing neurological conditions can also be a contraindication for CAR T-cell therapy.

How Does CAR T-Cell Therapy Work?

CAR T-cell therapy is one of the most promising cancer immunotherapy. It leverages the patient's immune system to target and eliminate cancer cells. The process involves the following steps – 

• T-Cell Extraction: T-lymphocytes (T-cells), crucial components of the adaptive immune system, are extracted from the patient's blood through apheresis, a well-established cell collection technique.
• CAR Engineering: These T-cells undergo genetic modification in a controlled laboratory environment. A genetically modified virus that cannot cause harm is used to develop a Chemical Antigen Receptor (CAR) molecule on the T-cell. The CAR is a specially designed protein. It empowers the engineered T-cells to specifically recognize and bind to antigens on the surface of targeted cancer cells.
• T-cell Expansion: Following CAR integration, the modified T-cells undergo expansion using appropriate culture conditions and growth factors. The potent anti-tumor T-cells are significantly multiplied and increased in number.
• Reinfusion and Targeting: The CAR T-cells are reintroduced into the patient's body via intravenous infusion. The CAR on the T-cell surface facilitates specific identification and binding to the target antigen on cancer cells. It triggers the activation of the CAR T-cells, initiating a potent cytotoxic response that eradicates the targeted cancer cells.
• Persistence and Memory: Ideally, a subset of the infused CAR T-cells can develop into memory T-cells. These memory cells persist within the patient, offering the potential for long-term immunological memory against the targeted cancer and potentially reducing the risk of relapse.

What are the Side Effects of CAR T-Cell Therapy?

Chemical Antigen Receptor (CAR) T-cell therapy is not suitable for everyone. You should consult an experienced cancer specialist to better understand whether you are an appropriate candidate for it. They will also educate you about a few potential complications the therapy may possess.

The most common complication of CAR T-cell therapy is CRS - cytokine release syndrome. CAR T-cells release chemicals called cytokines, which cause a reaction from the immune system. Signs and symptoms of CRS include:

• Fever and chills
• Pain in the muscles or joints
• Dizziness, lightheadedness, or headaches
• Fatigue
• Nausea, vomiting or diarrhea
• Rapid heartbeat
• Difficulty breathing
• Low blood pressure

CAR T-cell therapy may also cause harmful effects on the central nervous system. The signs and symptoms may include:

• Confusion
• Loss of balance 
• Unconsciousness 
• Tremors
• Seizures
• Trouble speaking or understanding

Other serious side effects that you may experience and require medical attention include:

• Allergic reactions
• Risk of infections, bleeding, or bruising
• Abnormal levels of minerals in the blood

What are the Advantages of CAR T-Cell Therapy?

• CAR T-cell therapy has shown exceptional efficacy in curing certain types of blood cancers, such as leukemia and lymphoma. Clinical trials have demonstrated exceptional response rates, even among patients who have not responded to traditional treatments like chemotherapy and radiation. 
• One advantage of this therapy is its targeted treatment approach. The engineered T-cells are programmed to precisely target cancer cells while sparing normal cells, reducing the collateral damage frequently associated with conventional treatments. 
• Patients undergoing this treatment have experienced long-term remission, offering them a chance at a substantially improved quality of life. 
• CAR T-cell therapy has a short treatment time. CAR T-cell therapies and stem cell transplants generally require only a single infusion of a few hours. However, while CAR T-cell therapies require less than two weeks of inpatient care, the entire course of stem cell treatment can take several months. Chemotherapy treatment regimens also require months to complete.
• Additionally, CAR T-cell therapy's potential is not limited to specific types of cancer. Current research explores its potential in treating various solid tumors, expanding its effectiveness across different cancer types. 
• Clinical trials have shown promising outcomes, with a notable increase in survival rates among CAR T-cell therapy patients. These findings indicate a pivotal shift in cancer treatment and management.

What is the Cost of CAR T-cell Therapy?

You must have heard about specific treatments that cost several crores. CAR T-cell therapy used to be one of them, but not anymore. While the cost of treatment in the USA and UK ranges from USD 3,00,000 to 5,00,000, it is much more affordable in India.

India has developed its own indigenous CAR T-cell therapy, NexCAR19. In October 2023, the CDSCO - Central Drugs Standard Control Organization approved its use for several blood cancers. NexCAR19 costs around INR 35-40 lakhs or USD 40,000 to 50,000, which is 80-90% less than what other countries offer. 

Outlook

CAR T-cell therapy has become a boom in cancer treatment. It is currently available to treat blood cancers, but with ongoing research, the future is promising for other cancers. CAR T-cell therapy most benefits people with cancer recurrences and those who cannot be managed with other treatment modalities. However, it is essential to remember that a few side effects might be related to the therapy. It is best to weigh the risks and benefits with a skilled oncologist who can help you decide better.