What is CAR T-Cell Therapy?
A patient's own T cells are engineered to find and attack cancer in a revolutionary new treatment called CAR T-cell therapy. With this therapy, specialized T cells from a patient's blood are removed and modified in the lab. Scientists genetically modify these T cells, called chimeric antigen receptor (CAR) T cells, to include a special receptor called a chimeric antigen receptor (CAR). This receptor recognizes and targets specific proteins on the surface of certain cancer cells. Once infused back into the patient, these CAR T cells can multiply in number and act as a "living drug" by finding and destroying cancer cells that have the matching target protein.
How Do CAR T Cells Work?
CAR T cells are a type of immunotherapy that involves taking T cells from a patient's blood and genetically modifying them to help the immune system more effectively detect and eliminate cancer cells. The T cells are collected from the patient through an apheresis process where blood is drawn from the patient, the T cells are separated and collected, and the remaining blood is returned to the patient. The extracted T cells are then genetically engineered to produce chimeric antigen receptors (CARs) on their surface. These CAR receptors allow the T cells to recognize and bind to a specific protein, known as an antigen, found on the surface of cancer cells. Once reinfused, the CAR T cells can multiply inside the patient in response to recognizing the cancer antigen, resulting in an amplified therapeutic effect from the living T cells.
Targeting CD19 for B Cell Malignancies
One of the most promising cancer antigens targeted by currently available CAR T-Cell Therapies is CD19, a protein commonly found on B cells and B cell cancers like leukemia and lymphoma. Two FDA-approved CAR T cell therapies, tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), target CD19. While CD19 is highly expressed on normal and malignant B cells, it is not found on other tissues, which allows CAR T cells to selectively target cancerous B cells while sparing other cells in the body. By attacking B cell cancers that express CD19, these therapies employ the patient's transformed T cells as a "living drug" to induce potent and sustained remissions in circumstances where other treatments have failed.
Managing Cytokine Release Syndrome
An expected side effect of CAR T cell therapy is cytokine release syndrome (CRS), which occurs as CAR T cells activate and multiply in response to encountering cancer cells. Large amounts of cytokines, or signaling proteins, are released which can cause a systemic inflammatory response with flu-like symptoms such as fever, nausea, vomiting and in severe cases, low blood pressure and organ dysfunction. Most cases of CRS are mild to moderate in severity and can be effectively managed with supportive care and anti-cytokine therapies like tocilizumab. Close monitoring is required after CAR T cell infusion to help identify and treat CRS promptly if it develops. While CRS poses risks if not properly managed, it also shows the therapy is working as intended by stimulating an active immune response against cancer.
Assessing Clinical Trial Results
Several early-phase clinical trials have demonstrated impressive response rates and durable remissions using CAR T cell therapies targeting CD19 in adults with relapsed or refractory leukemia and lymphoma. A 2017 study testing tisagenlecleucel in relapsed/refractory acute lymphoblastic leukemia patients reported an 83% complete remission rate and 6 month overall survival rate of 76%. Follow-up in later studies has shown responses can last for several years in some patients. For axicabtagene ciloleucel, pivotal trials in diffuse large B cell lymphoma reported objective response rates of 54% and complete response rates of 40%, outperforming standard therapies. While not all patients benefit, these results show CAR T cells can achieved deep and lasting responses in certain blood cancers where other options have failed. Larger follow up studies are ongoing to further optimize efficacy and durability.
Expanding CAR T Applications
Research is focusing on finding new cancer antigens that CAR T cells could target beyond just CD19 for B cell leukemias and lymphomas. This includes targeting CD20 for other B cell cancers, CD22, CD30 for Hodgkin's lymphoma, and tumor-associated antigens like mesothelin, HER2, and GD2 which are found in several solid tumors. Early clinical studies are evaluating CAR T therapies against these antigens in leukemia, myeloma, myelodysplastic syndrome, lung cancer, sarcoma, ovarian cancer and other solid tumors. Technical challenges remain for solid tumors due to greater difficulty in trafficking CAR T cells to antigen-positive cancer sites within solid tumor microenvironments. Researchers are pursuing combination strategies using CAR T cells together with other immunotherapies or cancer drugs to help overcome these obstacles. If successful, CAR T therapy could potentially be applicable to many additional cancer types beyond blood cancers in the future.
Managing Treatment Costs and Supply
The high costs of developing and manufacturing individualized its pose challenges to access and insurance coverage. Tisagenlecleucel carries a wholesale acquisition cost of $375,000 per treatment while axicabtagene ciloleucel costs $373,000 wholesale. However, given the potential for durable remissions, they may still prove cost-effective compared to prolonged alternative treatments in relapsed patients facing poor prognoses. Manufacturers are working to streamline production processes and build additional capacity to meet demand. Ensuring sustainable reimbursement models and supply will be important as more therapies receive approval and their use potentially expands to broader patient populations over time. Overall, CAR T cell therapy represents one of the most promising new approaches in oncology by directly harnessing a patient's own immune system against their cancer. With further development and broader application, it may transform outcomes for many cancer patients in the years ahead.
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Ravina Pandya, Content Writer, has a strong foothold in the market research industry. She specializes in writing well-researched articles from different industries, including food and beverages, information and technology, healthcare, chemical and materials, etc.
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