Chimeric Antigen Receptor T-cell therapy, or CAR-T therapy, stands at the forefront of revolutionary advancements in cancer treatment. This innovative approach harnesses the power of a patient’s own immune system to combat cancer cells. In CAR-T therapy, T cells, a type of immune cell, are genetically engineered to express a chimeric antigen receptor (CAR) on their surface. This receptor enables T cells to recognize and target specific proteins found on cancer cells. The modified T cells are then infused back into the patient, where they seek out and destroy cancerous cells, offering a promising avenue for the treatment of various forms of cancer. This article explores the fundamentals of CAR-T therapy and its groundbreaking potential in the realm of cancer therapeutics.
What is CAR T-cell therapy?
Chimeric Antigen Receptor (CAR) T-cell therapy enhances the cancer-fighting capabilities of your T-lymphocytes, also known as T-cells. These white blood cells play a crucial role in your immune system’s surveillance for potential threats, including cancer cells, by detecting surface proteins called antigens. Think of these antigens as identification markers on intruder cells.
Your T-cells come equipped with their own set of proteins called receptors, functioning like the anti-virus software on a computer. When the T-cell security team detects antigens on intruder cells, they use their receptors to intercept and neutralize these threats. Moreover, T-cells have the ability to eliminate the intruder cells altogether.
However, intruder antigens can employ protective measures to evade detection. They can disguise themselves to escape recognition by T-cells. CAR T-cell therapy is designed to empower your T-cells to overcome these antigen disguises and defenses.
In essence, CAR T-cell therapy acts as an upgrade for your immune system’s security software. By genetically modifying your T-cells to express Chimeric Antigen Receptors, the therapy ensures that your immune cells can effectively navigate past the disguises employed by cancer cells. This breakthrough approach enhances the precision and efficiency of T-cells in targeting and eliminating cancer, particularly proving to be a highly effective treatment for certain blood cancers. While long-term data is still being collected, CAR T-cell therapy holds great promise as a potent tool in the ongoing battle against cancer.
What cancers are treated with CAR T-cell therapy?
As of my last knowledge update in January 2022, CAR T-cell therapy has primarily been approved for the treatment of certain types of blood cancers. The specific cancers include:
- Acute Lymphoblastic Leukemia (ALL): CAR T-cell therapy has been notably successful in the treatment of pediatric and young adult patients with relapsed or refractory ALL.
- Diffuse Large B-cell Lymphoma (DLBCL): CAR T-cell therapy, specifically products like Kymriah (tisagenlecleucel) and Yescarta (axicabtagene ciloleucel), has been approved for the treatment of certain cases of DLBCL, including relapsed or refractory disease.
- Mantle Cell Lymphoma (MCL): Some CAR T-cell therapies have received approval for the treatment of relapsed or refractory MCL.
- Follicular Lymphoma: There are ongoing clinical trials exploring the effectiveness of CAR T-cell therapy in treating follicular lymphoma.
- Chronic Lymphocytic Leukemia (CLL): CAR T-cell therapy has shown promise in early clinical trials for CLL, and research is ongoing.
It’s important to note that research and clinical trials are continuously expanding to explore the application of CAR T-cell therapy in other types of cancers, including solid tumors. Since my information might not be up-to-date beyond January 2022, I recommend checking with the latest medical literature, clinical trial updates, or consulting with healthcare professionals for the most recent information on the use of CAR T-cell therapy in cancer treatment.
Car-t therapy in india
Department of Biotechnology supported First CAR-T cell therapy conducted at ACTREC, Tata Hospital in Mumbai
CAR-T cell therapy has emerged as a groundbreaking advancement in cancer treatment, demonstrating promising results in global clinical trials, particularly for patients in the end stages of diseases such as Acute Lymphocytic Leukemia. Despite its therapeutic potential, CAR-T therapy is currently unavailable in India, with each patient’s treatment costing approximately 3-4 crore INR.
The high cost is primarily attributed to the manufacturing complexity of the therapy. To address this challenge and facilitate the development of cost-effective CAR-T cell technology, initiatives have been taken by BIRAC (Biotechnology Industry Research Assistance Council) and DBT (Department of Biotechnology). Specialized calls have been launched in the past two years to invite proposals for the advancement of CAR-T cell technology against cancer and other diseases.
A significant milestone was achieved on June 4, 2021, when the first CAR-T cell therapy in India, a type of gene therapy, was conducted at the Bone Marrow Transplant unit at ACTREC, Tata Memorial Center in Mumbai. The CAR-T cells were designed and manufactured at the Bioscience and Bioengineering department of IIT Bombay.
This groundbreaking achievement is partly supported by the BIRAC-PACE scheme. The collaboration between Tata Memorial Hospital, Mumbai, and IIT Bombay has led to the initiation of a Phase I/II clinical trial for the CAR-T product, supported by DBT/BIRAC through the National Biopharma Mission.
The central government’s National Biopharma Mission-BIRAC has allocated 19.15 crore INR to the team for conducting the first-in-human phase 1/2 clinical trial of CAR-T cells. Dr. (Surg Cdr) Gaurav Narula, Professor of Paediatric Oncology and Health Sciences, along with his team from TMC, Mumbai, is leading the clinical trials. The novel CAR-T cells, acting as drugs, were manufactured by Prof Rahul Purwar and his team at the Bioscience and Bioengineering department of IIT Bombay. The project involved design, development, and extensive pre-clinical testing in collaboration with Tata Memorial Center, Mumbai.
IIT Bombay’s director, Subhasis Chaudhuri, expressed delight in the institute’s contribution, emphasizing the potential for the sophisticated therapy to save lives by providing an affordable treatment option in India, pending successful clinical trials. The National Biopharma Mission is also supporting the development of manufacturing facilities for Lentiviral vectors and cGMP facilities for T-cell transduction, further advancing CAR-T cell technology for various diseases, including acute lymphocytic leukemia, multiple myeloma, glioblastoma, hepatocellular carcinoma, and type-2 diabetes.
Advantages of CAR T-Cell Therapy
Chimeric Antigen Receptor (CAR) T-cell therapy offers several advantages in the treatment of certain cancers:
- Precision Targeting: CAR T-cell therapy is designed to target specific antigens present on cancer cells. This precision allows for a more targeted attack on cancer, minimizing damage to healthy cells.
- Personalized Treatment: The therapy involves harvesting a patient’s own T-cells, genetically modifying them, and then infusing them back into the patient. This personalized approach harnesses the individual’s immune system for a tailored response.
- Treatment for Relapsed/Refractory Cases: CAR T-cell therapy has shown remarkable efficacy in treating cancers that have relapsed or are refractory to other treatments, providing a viable option for patients with limited therapeutic alternatives.
- Potential for Long-Term Remission: Some patients treated with CAR T-cell therapy have experienced sustained remissions, offering the potential for long-term control or even eradication of the cancer.
- Single Infusion Treatment: Unlike traditional treatments that may require prolonged courses, CAR T-cell therapy often involves a single infusion. This can reduce the overall treatment burden on patients.
- Adaptable to Different Cancer Types: While initially approved for certain blood cancers, CAR T-cell therapy is being explored for various cancer types. This adaptability underscores its potential as a versatile immunotherapy.
- Ongoing Research and Advancements:The field of CAR T-cell therapy is dynamic, with ongoing research leading to advancements in technology, safety profiles, and effectiveness. This continual evolution enhances the therapy’s potential over time.
- Reduced Relapse Rates in Some Cases: In certain cancers, CAR T-cell therapy has demonstrated lower relapse rates compared to standard treatments, indicating a durable and robust response in some patients.
- Minimal Residual Disease (MRD) Eradication: CAR T-cell therapy has shown the capability to eliminate minimal residual disease, which refers to small amounts of cancer cells that may remain after initial treatment and can contribute to relapse.
- Potential for Off-the-Shelf Products: Research is underway to develop “off-the-shelf” CAR T-cell products, where engineered T-cells from healthy donors can be used for treatment, offering a more readily available and scalable option.
While these advantages highlight the promise of CAR T-cell therapy, it’s important to note that challenges and potential side effects, such as cytokine release syndrome (CRS) and neurotoxicity, also exist. Ongoing research aims to optimize the therapy and address these considerations to improve patient outcomes.
Potential Side Effects of CAR T-Cell Therapy
Chimeric Antigen Receptor (CAR) T-cell therapy, while showing promise in treating certain cancers, can be associated with various side effects. It’s important to note that the severity and occurrence of these side effects can vary among individuals. Common side effects include:
- Cytokine Release Syndrome (CRS): CRS is a systemic inflammatory response that can occur when the CAR T-cells become activated and release a large amount of cytokines. Symptoms range from mild, flu-like symptoms to more severe complications, including high fever, low blood pressure, and organ dysfunction.
- Neurological Toxicity: Some patients may experience neurological side effects, ranging from mild confusion and tremors to more severe conditions like seizures and cerebral edema.
- Febrile Neutropenia: A drop in the number of neutrophils (a type of white blood cell) can lead to febrile neutropenia, making patients more susceptible to infections. Fever during neutropenia requires prompt medical attention.
- B Cell Aplasia: CAR T-cell therapy may lead to the depletion of normal B cells, increasing the risk of infections. Regular monitoring and potential immunoglobulin replacement therapy may be needed.
- Hypogammaglobulinemia: Reduced levels of immunoglobulins (antibodies) can occur, increasing susceptibility to infections. This may require ongoing monitoring and treatment.
- Tumor Lysis Syndrome: Rapid destruction of cancer cells can release substances into the bloodstream, potentially causing metabolic imbalances. This can lead to complications such as kidney dysfunction and electrolyte abnormalities.
- Hematologic Toxicities: Low blood cell counts, including anemia, thrombocytopenia, and neutropenia, can occur as a result of the impact on normal blood cell production.
- Organ Toxicities: In some cases, CAR T-cell therapy may cause organ-specific toxicities, such as liver dysfunction or cardiac issues. Close monitoring is essential.
- Secondary Cancers: There is a potential risk of developing secondary cancers as a result of the genetic modifications made during CAR T-cell therapy. Long-term monitoring is crucial.
It’s important for patients to be closely monitored during and after CAR T-cell therapy, and healthcare providers will manage side effects as they arise. The severity and duration of these side effects can vary, and healthcare teams are well-prepared to address and manage them to ensure the best possible outcomes for patients undergoing CAR T-cell therapy.
The Bottom Line
CAR T-cell therapy emerges as a transformative force in the fight against cancer. Its personalized approach, leveraging the body’s own immune system to target and destroy malignant cells, marks a pivotal shift in the landscape of cancer treatment. With its ability to induce durable responses in certain types of cancers, CAR T-cell therapy stands as a beacon of innovation, offering renewed hope for patients who once faced limited treatment options. As research and development in this field continue to advance, the future holds the promise of even more refined and widely applicable CAR T-cell therapies, ushering in a new era where the complexities of cancer are met with increasingly sophisticated and effective solutions.
What is CAR T-cell therapy?
CAR T-cell therapy is a groundbreaking immunotherapy approach that involves genetically modifying a patient’s own T cells to express chimeric antigen receptors (CARs). These receptors enable T cells to recognize and attack cancer cells more effectively.
What is the future outlook for CAR T-cell therapy?
The field of CAR T-cell therapy is rapidly evolving. Ongoing research aims to expand its application to a broader range of cancers and improve its safety and efficacy. The future holds promise for further advancements and refinements in this innovative cancer treatment approach.
Are there eligibility criteria for CAR T-cell therapy?
Eligibility criteria depend on factors such as the type of cancer, previous treatments, and overall health. Healthcare professionals assess each patient individually to determine suitability for CAR T-cell therapy.
How effective is CAR T-cell therapy?
CAR T-cell therapy has shown remarkable effectiveness, especially in patients with certain types of blood cancers who have not responded to conventional treatments. Response rates and durability of response vary among individuals and cancer types.
Is CAR T-cell therapy a one-time treatment?
In many cases, CAR T-cell therapy is a one-time treatment. The genetically modified T cells can persist in the body and continue to target cancer cells. However, additional treatments or supportive therapies may be needed in some cases.