CAR T-Cell Therapy

CAR T cell therapy is an innovative treatment for some cancers, including leukemia, lymphoma, and multiple myeloma. It works by changing a patient’s T cells, which are part of the immune system so that they can detect and fight cancer cells more effectively. Scientists genetically change these T cells in a lab to express unique receptors known as chimeric antigen receptors (CARs), which allow them to target particular proteins in cancer cells.

This treatment effectively transforms the patient’s immune cells into superpowered cancer fighters. CAR T cell therapy, which harnesses the body’s defences, represents a possible new approach to cancer treatment, particularly when other therapies have failed. While research continues, CAR T cell treatment has shown significant effectiveness in improving outcomes for people facing certain blood cancers.

India’s approval of NexCAR19, its first CAR-T cell therapy, marks a significant advance in cancer treatment. CAR-T therapy, which is customized to each patient, has shown promise in the treatment of advanced leukaemia’s and lymphomas. Affordability remains a concern, with domestic medicine costing around a tenth of US treatment but still exceedingly costly for many at over $48000.

Working of CAR T-Cell Therapy

CAR T-cell therapy is an advanced cancer treatment that makes use of the immune system’s abilities. It works as:

• T-cell collection: Leukapheresis is used to collect T-cells from the patient’s blood, which are important components of the immune system.
• Genetic modification: In a lab, these T-cells are genetically modified with a harmless virus to add chimeric antigen receptors (CARs) on their surface. These CARs allow T cells to detect particular proteins in cancer cells.
• Expansion and modification: To increase the quantity of modified T-cells, they are produced and multiplied in the laboratory.
• Infusion back into the patient: Once a sufficient number of CAR T-cells have been obtained, they are reintroduced into the bloodstream of the patient.
• Targeting and destruction: The CARs on these modified T-cells allow them to detect and attach to particular antigens found on cancer cells. After binding, CAR T-cells become activated, generating an immune response that destroys cancer cells.
• Proliferation and memory: Some modified T-cells continue to multiply in the body, acting as “memory” cells. These memory cells may provide continual surveillance, allowing for long-term protection against cancer and lowering the chance of recurrence.

Suitable Candidate for CAR-T Cell Therapy

The most suitable candidate for CAR T-cell therapy usually has:

• Blood Cancer: CAR T-cell therapy is generally used to treat hematopoietic cancers such as acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), and others.
• Specific Antigen Expression: Cancer cells should express antigens targeted by the chimeric antigen receptor (CAR). This is important for the modified T-cells to detect and destroy cancer cells efficiently.
• Previous Treatment Failure: CAR T-cell therapy is often recommended for patients who have not reacted well to traditional treatments such as chemotherapy or have had a recurrence.

CAR T-cell therapy may be suggested for children and young people with B cell ALL under the age of 25, especially in cases of treatment resistance or recurrence after stem cell transplant.It may be effective for people with particular types of lymphoma, such as diffuse large B cell lymphoma or mantle cell lymphoma, who have not responded to previous treatments or have had recurrence.

Cancers Treated using CAR-T Cell therapy

CAR T-cell therapy has emerged as a viable treatment option for blood cancers that do not respond to chemotherapy or other traditional treatments. CAR T-cell therapies are used for the following cancers:

• B-cell acute lymphoblastic leukemia (ALL)
• B-cell non-Hodgkin lymphoma (including subtypes like diffuse large B-cell lymphoma, follicular lymphoma with DLBCL, and high-grade B-cell lymphoma)
• Primary mediastinal large B-cell lymphoma
• Mantle cell lymphoma
• Multiple myeloma

FDA-approved CAR T-cell therapies for these cancers include drugs like Kymriah®, Yescarta®, Breyanzi®, Tecartus®, Abecma®, and others.

Risks Associated with CAR-T Cell Therapy

• Cytokine Release Syndrome (CRS): It is a potentially dangerous side effect of CAR T-cell treatment. It involves the rapid release of cytokines into the circulation, resulting in an overactive immune response. CRS symptoms range from mild flu-like symptoms such as fever, chills, and weakness to more severe presentations such as hypotension, respiratory distress, and brain abnormalities. CRS is managed by closely monitoring patients’ symptoms and providing supportive treatment, including the administration of tocilizumab in severe cases, to reduce cytokine-mediated inflammation and organ failure.
• Neurological Toxicities: CAR T-cell therapy may cause harmful effects on the central nervous system. These symptoms might include disorientation, seizures, tremors, aphasia, and loss of balance. These symptoms might be due to immune-mediated inflammation or the direct actions of cytokines on brain cells. Management includes carefully monitoring for neurological abnormalities and, if required, using corticosteroids to decrease inflammation and seizure medicines.
• Tumor Lysis Syndrome (TLS): It is the fast breakdown of cancer cells after CAR T-cell treatment, resulting in the release of intracellular contents into the circulation. This can lead to metabolic abnormalities such as hyperuricemia, hyperkalemia, and hyperphosphatemia, which can cause kidney failure and cardiac problems. To avoid and treat TLS-related problems, vigorous hydration, and drug treatment to decrease uric acid levels are suggested, as is continuous monitoring of electrolyte levels and kidney function.
• Anaphylaxis: It is a rare yet severe allergic reaction that can develop after CAR T-cell treatment. In rare cases, patients may experience hives, facial swelling, hypotension, and respiratory distress, indicating a systemic immunological reaction to the treatment. Anaphylaxis is an uncommon but potentially fatal condition that needs rapid medical care and action.
• On-target, Off-tumor Toxicity: On-target, off-tumor CAR T-cell treatment can cause unintentionally harm to healthy tissues that express the same antigen, known as on-target, off-tumor toxicity. While the therapy is intended to exclusively target cancer cells, it may mistakenly harm normal cells that express the targeted antigen, especially in important organs such as the heart, lungs, or liver. This off-target impact might lead to serious problems and endanger the patient’s health.
• B-Cell Aplasia: CAR T-cell treatment can cause B-cell aplasia, which occurs when both cancerous and normal B cells are reduced. This depletion decreases the body’s ability to manufacture antibodies, making the patient more susceptible to infections. CAR T-cell treatment changes the immune system’s balance by killing both normal and cancerous B cells, necessitating continuous monitoring and, in certain cases, immunoglobulin replacement therapy to avoid infection.
• Other Side Effects: CAR T-cell therapy may cause unexpected side effects beyond the risks stated above. These include an increased risk of infection owing to B-cell depletion, high levels of uric acid in the blood caused by the fast breakdown of cancer cells, and potential long-term consequences that require continuous monitoring and care.

Procedure for CAR-T Cell Therapy in India

• Patient Evaluation: Before receiving CAR T-cell treatment, patients are evaluated carefully for their medical history, overall health, and particular cancer features to determine eligibility and analyse possible risks.
• Cell Collection (Leukapheresis): The procedure of collecting T-cells from a patient’s blood is known as leukapheresis. This involves collecting blood from a vein, isolating the T-cells with apheresis technology, and then returning the other blood components to the patient’s circulation.
• Cell Modification: In the laboratory, collected T-cells are genetically changed to express the chimeric antigen receptor (CAR), allowing them to better detect and target cancer cells.
• Cell Expansion: The modified T-cells are produced and increased in the laboratory to produce sufficient numbers for therapeutic purposes. This stage involves allowing the CAR T-cells to proliferate and expand until they reach a suitable cell count.
• Lymphodepletion: Before CAR T-cell infusion, patients are commonly subjected to lymphodepletion, which includes the use of chemotherapy to decrease existing immune cells and provide space for the infused CAR T-cells to grow successfully within the body.
• CAR T-Cell Infusion: The transformed and enlarged CAR T-cells are then returned to the patient’s circulation. This method is commonly performed via intravenous infusion, allowing CAR T-cells to circulate throughout the body and target cancer cells.
• Monitoring: After CAR T-cell infusion, patients are continuously monitored for potential side effects such as cytokine release syndrome (CRS) and neurologic toxicities. Continuous monitoring allows the early diagnosis and control of any unfavourable reactions.

Precautions and Aftercare

• Manage Side Effects: Prompt care of side effects such as fever, chills, and neurological symptoms is essential for reducing complications and ensuring patient safety.
• Infection Prevention: Because of the temporary immune suppression, infection prevention measures are carried out to limit the risk of opportunistic infections.
• Preventive medications: Some patients may be given medications to avoid specific side effects such as cytokine release syndrome, and to help them recover after treatment.

Benefits of CAR-T Cell Therapy

• Remarkable Efficacy: CAR T-cell therapy has shown remarkable efficacy in treating specific blood cancers, especially in individuals who have not responded to traditional treatments such as chemotherapy.
• Targeted Treatment: Engineered T-cells specifically target cancer cells, reducing the harm to healthy tissues that are common in standard treatments.
• Long-term Remission: Patients experience periods of no cancer recurrence, which improves their quality of life.
• Potential for Diverse Applications: CAR T-cell therapy has the potential for a wide range of applications, as research investigates its efficacy in many cancer types.
• Improved Survival Rates: Clinical trials show better survival rates, giving hope to patients with resistant cancers.

CAR-T Cell therapy Cost in India

The cost of indigenous CAR-T cell therapy in India is about $48,000. This cost is much cheaper than comparable medicines available abroad, which may cost up to INR 4 crore, or $480,000. The emergence of more inexpensive CAR T-cell therapy options in India offers hope to people seeking advanced cancer treatment without suffering the financial hardship of traveling overseas.

CAR-T Cell Therapy Success Rate in India

CAR-T cell therapy in India has success rates ranging from 30% to 80%, depending on the quality of the hospital doing the treatment. The success rate varies depending on the skill of doctors, the quality of infrastructure and resources available, and patient-specific characteristics. Hospitals with vast expertise and specialized facilities have a better success rate in CAR-T cell treatment, providing promising results for patients suffering from hematologic malignancies.

Top Hospitals for CAR-T Cell Therapy in India

• Manipal Hospitals, Bengaluru
• Max Super Speciality Hospital, New Delhi
• Tata Memorial Centre, Mumbai
• Fortis Memorial Research Institute, Gurugram
• Apollo Hospitals, Chennai
• Rajiv Gandhi Cancer Institute and Research Centre, Delhi
• Medanta – The Medicity, Gurugram
• Kokilaben Dhirubhai Ambani Hospital, Mumbai
• Artemis Hospital, Gurugram