Car T Cell Therapy: A Revolution in Cancer Treatment
3 Apr, 2025
What is CAR T Cell Therapy? CAR T cell therapy is a type of immunotherapy that employs chimeric antigen receptor (CAR) T cells to fight cancer. In this therapy, a patient's own T cells are collected and genetically modified to express an engineered receptor called a chimeric antigen receptor (CAR) on their surface. This CAR redirects the T cells to specifically target and eliminate cancer cells carrying a specific tumor antigen. Once re-engineered to express the CAR, billions of copies of the modified cells are grown in the laboratory and infused back into the patient to seek out and destroy cancer cells. How Does it Work? In Car T Cell Therapypy, T cells are removed from a patient's blood and sent to a manufacturing facility. There, the DNA of the patient's T cells is modified using a virus or other vector to cause the cells to produce a specific CAR on their surface. The CAR incorporates the high affinity binding portion of an antibody that recognizes a tumor antigen, fused to signaling domains of the T cell receptor complex. This redirects the T cell to target the tumor antigen. After genetic engineering, the CAR T cells are grown and expanded in large numbers before being infused back into the patient. Once inside the body, the CAR T cells multiply and persist, helping the patient's immune system to recognize and eliminate cancer cells carrying the target antigen. Target Antigens The two most widely targeted tumor antigens in CAR T cell therapies currently approved are CD19 and BCMA. CD19 is expressed on B cells and B cell malignancies like leukemia and lymphoma. Therapies targeting CD19 have shown significant responses in clinical trials for leukemia and lymphoma. BCMA, or B cell maturation antigen, is primarily expressed on plasma cells and multiple myeloma cells. BCMA-targeted CAR T therapies have demonstrated promise in treating multiple myeloma in early and mid-stage clinical trials. Other tumor antigens being investigated as targets in newer CAR T therapies include CD20, CD22, CD30, CD33, CD138, CEA, EGFRvIII, GD2, and others. Manufacturing Process The manufacturing of CAR T cell therapies involves multiple complex steps carried out under strict quality controls. It begins with leukapheresis to collect the patient's T cells, which are then shipped to a manufacturing facility. There, the T cells are activated and expanded in number, and the CAR gene is introduced using a viral or non-viral vector. The engineered CAR T cells are grown in bioreactors and purified through multiple processing steps. Quality testing confirms the correct genetic modification, sterility, and cellular composition. Finally, the manufactured CAR T cell product is formulated, frozen, and stored for shipment back to the clinical site for infusion into the patient. The entire process from collection to delivery can take 3-4 weeks to complete. Leading Therapies Several CAR T cell therapies have gained FDA approval in recent years based on compelling results in clinical trials. Yescarta and Kymriah were the first CAR T cell therapies to gain FDA approval in 2017. Yescarta targets CD19 for the treatment of certain types of large B-cell lymphoma, while Kymriah targets CD19 for the treatment of pediatric and young adult patients with B-cell precursor acute lymphoblastic leukemia. Breyanzi, also a CD19-targeted therapy, was approved in 2021 for certain types of large B-cell lymphoma. Abecma, a BCMA-targeted therapy, received FDA approval in 2021 for multiple myeloma. These first-generation CAR T cell therapies have achieved complete response rates of 40-60% in late-stage clinical trials, representing a major breakthrough. However, newer improvements are being studied to enhance their safety profile and durability of response. Challenges and Future Directions While CAR T cell therapies have revolutionized cancer treatment, there remain challenges to optimize their effectiveness and safety. Toxic side effects like cytokine release syndrome and neurotoxicity require careful management. The therapies are also quite expensive, costing upwards of $373,000 per treatment in the U.S. Limited persistence or duration of response is another issue, with some patients relapsing months later. Researchers are working on second and third generation CAR T cell therapies with built-in safety switches to stop tumor targeting if side effects occur. New strategies to augment CAR T cell persistence and reduce relapse risk are under active investigation. The burgeoning field of allogeneic "off-the-shelf" CAR T cells using engineered donor cells, as well as combination therapies with checkpoint inhibitors and bispecific antibodies, hold promise to make these revolutionary treatments safer, more affordable, and potentially curative for more cancer patients in the future.
Vaagisha brings over three years of expertise as a content editor in the market research domain. Originally a creative writer, she discovered her passion for editing, combining her flair for writing with a meticulous eye for detail. Her ability to craft and refine compelling content makes her an invaluable asset in delivering polished and engaging write-ups.
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