Sansad TV Vishesh: CAR T-Cell Therapy | Current Affairs & Hindu Analysis: Daily, Weekly & Monthly - UPSC PDF Download

What is CAR T-Cell Therapy?

CAR T-cell Therapy, also known as Chimeric Antigen Receptor T-cell Therapy, represents a groundbreaking form of immunotherapy that leverages the patient's immune system to combat cancer. Often dubbed as 'living drugs', CAR-T cell therapies have gained approval for treating leukaemias and lymphomas, which originate from white blood cells and the lymphatic system, respectively. Since 2017, six CAR T-cell therapies have received FDA approval, primarily targeting blood cancers like lymphomas, certain forms of leukemia, and most recently, multiple myeloma.

The treatment process involves several intricate steps:

• T Cell Collection: T cells, vital components of the immune system responsible for fighting infections, are harvested from the patient's blood through a process called Apheresis.
• Genetic Engineering: In a laboratory setting, these T cells undergo genetic modification to express a specialized protein known as a Chimeric Antigen Receptor (CAR) on their surface. This CAR is engineered to recognize and bind to specific antigens found on cancer cells.
• Cell Expansion: The modified T cells are then multiplied in large quantities within the lab.
• Infusion: The expanded CAR-T cells are reintroduced into the patient's bloodstream through infusion. These engineered cells can then identify and attack cancer cells expressing the targeted antigen.

In India, significant progress has been made in the development of CAR-T cell therapy. NexCAR19, the country's first indigenous CAR-T cell therapy for cancer, was collaboratively developed by ImmunoACT, Indian Institute of Technology Bombay (IIT-B), and Tata Memorial Hospital. In October 2023, the Central Drugs Standard Control Organisation (CDSCO) approved the commercial use of NexCAR19 for certain blood cancers, marking a milestone as the first CAR-T cell therapy to receive CDSCO approval.

CAR-T therapy offers several potential benefits:

• High Remission Rates: In some cases, particularly for patients with advanced cancers resistant to other treatments, CAR-T therapy can achieve high rates of complete remission.
• Targeted Treatment: CAR T-cell therapy precisely targets cancer cells expressing the target antigen, sparing healthy cells and potentially reducing side effects compared to traditional treatments like chemotherapy.
• High Efficacy: Notably effective in certain blood cancers such as Acute Lymphoblastic Leukemia (ALL), Chronic Lymphocytic Leukemia (CLL), and Non-Hodgkin Lymphoma (NHL), CAR T-cell therapy has demonstrated impressive efficacy rates.
• Single Treatment: Often requiring just one infusion of engineered T cells, CAR T-cell therapy can provide long-lasting therapeutic effects, unlike chemotherapy, which may necessitate multiple cycles of treatment.
• Personalized Medicine: By tailoring the therapy to each patient's specific cancer antigens, CAR T-cell therapy represents a form of personalized medicine with potential applications across various cancer types.

What are the Challenges Regarding CAR T-Cell Therapy?

• Cytokine Release Syndrome (CRS): CRS is a systemic inflammatory response triggered by the activation and proliferation of CAR-T cells in the body.
  • Symptoms can range from mild, flu-like symptoms to severe manifestations such as high fever, low blood pressure, and organ dysfunction. In severe cases, CRS can be life-threatening if not promptly managed.
• Cytopenias: Treatment with CAR T-cell therapy can lead to cytopenias, including low levels of red blood cells (anemia), white blood cells (neutropenia), and platelets (thrombocytopenia).
  • These conditions can increase the risk of infections, bleeding, and other complications.
• Immune Effector Cell-Associated Syndrome (ICANS): ICANS encompasses a range of neurological symptoms associated with CAR T-cell therapy, including confusion, aphasia, and seizures. ICANS can occur concurrently with CRS or independently and may require close monitoring and intervention.
• Tumor Lysis Syndrome (TLS): In some cases, rapid destruction of cancer cells following CAR T-cell therapy can lead to the release of intracellular contents into the bloodstream, causing metabolic abnormalities such as hyperkalemia, hyperuricemia, and acute kidney injury.

Way Forward

Cost Reduction:

• Explore strategies to reduce the high cost of CAR T-cell therapy, such as negotiating pricing agreements with manufacturers, implementing value-based pricing models, and investing in research and development to optimize manufacturing processes and increase efficiency.

Management of Cytokine Release Syndrome (CRS):

• Develop standardized protocols for the early detection and management of CRS, including the use of immunosuppressive medications (such as tocilizumab) to dampen the inflammatory response.
• Enhance healthcare provider education and training on recognizing and managing CRS, including the importance of close monitoring and timely intervention.

Management of Cytopenias:

• Implement strategies to mitigate the risk of cytopenias associated with CAR T-cell therapy, such as supportive care measures (e.g., blood transfusions, growth factors) and dose optimization to minimize hematologic toxicity while maintaining therapeutic efficacy.

Management of Immune Effector Cell-Associated Syndrome (ICANS):

• Develop standardized approaches for the assessment and management of ICANS, including neurological monitoring and interventions (e.g., corticosteroids) for symptomatic relief.
• Invest in research to better understand the underlying mechanisms of ICANS and identify predictive biomarkers to guide risk stratification and early intervention.

Prevention and Management of Tumor Lysis Syndrome (TLS):

• Implement protocols for the prevention and early detection of TLS, including hydration strategies and the use of urate-lowering agents.
• Monitor patients closely for signs of TLS during CAR T-cell therapy and provide prompt intervention to mitigate metabolic abnormalities and prevent renal complications.