CAR T-Cell Therapy in Delhi, India

CAR T-cell therapy is a form of cell therapy that harnesses the body's immune system to combat cancer. This revolutionary treatment involves modifying and reprogramming a patient's T-cells—white blood cells critical to the immune system—to recognise and attack specific cancer cells. The process begins by extracting a patient's T-cells and genetically engineering them in a laboratory to express chimeric antigen receptors.

Chimeric Antigen Receptors (CARs) are artificial receptors designed to redirect T-cells in the immune system to recognise and target specific proteins or antigens found on cancer cells.

Here's a simplified breakdown of how CAR T-cell therapy works:

• Collection of T-cells: A patient's T-cells are extracted from their blood through a process called leukapheresis.
• Genetic modification: In a laboratory setting, these T-cells are modified using a viral vector (a harmless virus) to introduce genes that encode a chimeric antigen receptor (CAR) on their surface. This CAR is designed to recognise specific proteins, called antigens, found on the surface of cancer cells.
• Expansion and modification: The modified T-cells are cultured and multiplied to increase their numbers.
• Infusion back into the patient: Once a sufficient number of these engineered CAR T-cells is obtained, they are infused back into the patient's bloodstream. The CAR T-cells are now equipped to recognise and target the specific cancer cells they were engineered to attack.
• Targeting and destruction: The CAR on the surface of these modified T-cells helps them recognise and bind to specific antigens on the cancer cells. Upon binding, the CAR T-cells become activated, triggering an immune response leading to the destruction of the cancer cells.
• Proliferation and memory: Some of these engineered T-cells continue to proliferate in the body and persist as "memory" cells. These memory cells may provide ongoing surveillance, offering the potential for long-term immunity against the cancer and reducing the likelihood of cancer recurrence.

This therapy has shown promising results in certain types of leukaemia and lymphoma. However, it's essential to note that CAR T-cell therapy is a complex and personalised treatment that may have significant side effects, including cytokine release syndrome (CRS) and neurologic toxicity, which can be severe in some cases.

Who is the right candidate for CAR T-Cell Therapy?

The ideal candidate for CAR T-cell therapy typically has:

• Blood Cancer: CAR T-cell therapy is primarily used for haematologic malignancies like acute lymphoblastic leukaemia (ALL), diffuse large B-cell lymphoma (DLBCL), and others.
• Specific Antigen Expression: The cancer cells should express specific antigens targeted by the chimeric antigen receptor (CAR). This is crucial for the modified T-cells to recognise and attack the cancer cells.
• Previous Treatment Failure: CAR T-cell therapy is often considered for patients who have not responded well to standard treatments like chemotherapy or have experienced relapse.

Contraindications for CAR T-Cell Therapy

Contraindications for CAR T-cell therapy may include:

• Severe Organ Dysfunction: Patients with severe organ dysfunction may not be suitable candidates.
• Active Infections: Active infections could increase the risk of complications.
• Neurological Conditions: Certain pre-existing neurological conditions may pose a contraindication.

Preparation Before the CAR T-Cell Therapy

• Patient Evaluation: A thorough evaluation of the patient's medical history, overall health, and specific cancer characteristics is conducted.
• Cell Collection (Leukapheresis): T-cells are collected from the patient's blood through a process called leukapheresis.
• Cell Modification: The collected T-cells are genetically modified in the laboratory to express the chimeric antigen receptor (CAR).
• Cell Expansion: The modified T-cells are cultured and expanded to generate a sufficient quantity for therapeutic use.

Procedure

• Lymphodepletion: Before CAR T-cell infusion, patients often undergo lymphodepletion, which involves the administration of chemotherapy to deplete existing immune cells and create space for the infused CAR T-cells to proliferate.
• CAR T-Cell Infusion: The modified T-cells are then infused back into the patient's bloodstream.
• Monitoring: Patients are closely monitored for potential side effects, including cytokine release syndrome (CRS) and neurologic toxicities.

Precautions and Aftercare

• Manage Side Effects: Promptly address and manage any side effects, such as fever, chills, and potential neurological symptoms.
• Infection Prevention: Infection prevention measures are taken since the immune system can be temporarily weakened.
• Preventive Medications: Some patients may be prescribed medications to prevent certain side effects, such as cytokine release syndrome.

Key Benefits of CAR T-Cell Therapy

• Remarkable Efficacy: CAR T-cell therapy has demonstrated unprecedented success in treating some types of blood cancers, such as certain forms of leukaemia and lymphoma. Clinical trials have shown exceptional response rates, even in patients who have not responded to traditional treatments like chemotherapy and radiation.
• Targeted Treatment: The engineered T-cells are programmed to precisely target cancer cells while sparing healthy cells, reducing the collateral damage often associated with conventional treatments.
• Long-term Remission: Patients who have undergone this treatment have experienced sustained periods free from cancer recurrence, offering them a chance at a substantially improved quality of life.
• Potential for Diverse Applications: The application of CAR T-cell therapy is not limited to specific types of cancer. Ongoing research is exploring its potential in treating various solid tumours, expanding the scope of its effectiveness across different cancer types.
• Improved Survival Rates: Clinical trials have shown promising outcomes, with a notable increase in survival rates among patients who have undergone CAR T-cell therapy. These findings signify a pivotal shift in the way cancer is being treated and managed.

While the benefits of CAR T-cell therapy are substantial, there are challenges to overcome. These include managing potential side effects, optimising its efficacy in solid tumours, and addressing the high costs of this cutting-edge treatment.

The future of CAR T-cell therapy appears promising, with ongoing research focusing on refining the technique, broadening its applicability, and making it more accessible to a larger population of cancer patients. The incorporation of CRISPR, a gene-editing therapy, combined with cellular therapy (recently approved for the treatment of sickle cell disease by the US FDA) is a watershed event in the field of cell and gene therapy for both cancerous and non-cancerous genetic conditions.

CAR T-cell therapy stands as a beacon of hope in the realm of cancer treatment, showcasing remarkable success in addressing certain types of cancer and offering new possibilities for patients who have exhausted conventional treatment options.

Review

Reviewed by Dr. Esha Kaul - Director - Medical Oncology (Haematology, Hemato - Oncology, BMT), Bone Marrow Transplant, Cancer Care / Oncology on 8-May-2024.

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