Acute Lymphoblastic Leukemia Treatment with CAR-T Cell Immunotherapy
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Katayoon Rahmani,1,*
1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
- Introduction: ALL, also known as lymphocytic leukemia, is a malignancy that affects both children and adults. Malignant transformation and proliferation occur in lymphoid progenitor cells in the bone marrow, blood, and extramedullary locations. The majority of ALL cases are of the precursor B-cell type, while T-cell neoplasm is a rare and exceedingly aggressive phenotype that affects somewhat more adults than children. CAR Structures are synthetic receptors that are made up of four basic parts: an external target antigen binding domain, a hinge region, a transmembrane domain, and one or more intracellular signaling domains. Isolation of donor T cells is followed by effective activation, gene transfer of the CAR construct, CAR-T cell multiplication, phenotyping, and quality check analysis during the process of CAR-T cell therapy as an emerging treatment approach. Patients' (autologous) or healthy donors (allogeneic) peripheral blood mononuclear cells are used to make leukocytes (PBMCs). Purifying autologous antigen-presenting cells (APCs) from patients or donors, or beads coated with anti-CD3/anti-CD28 monoclonal antibodies, or anti-CD3 antibodies alone or in combination with feeder cells and growth factors, such as IL-2, are used to separate T cell subsets, which are then activated using specific antibodies.
- Methods: In this study, Science Direct, Springer, Google Scholar, and PubMed content were used to evaluate the treatment of acute lymphoblastic leukemia with CAR-T cell immunotherapy.
- Results: As a result, CAR T-cell therapies have several advantages over chemotherapy. Patients whose cancer recurs after numerous therapies may benefit from CAR T-cell therapy, which can help them achieve long-term remissions. Some cancer patients can go for long periods without their disease progressing. CAR T-cell therapies have a variety of advantages, including fewer infusions, a shorter treatment period, and faster recovery. CAR T-cell therapies benefit from living cells, which can multiply in the patient's body and give long-term memory. As a result, when there is a relapse, existing long-lived CAR T-cells can recognize and kill cancer cells. After a single infusion of CAR T-cell treatments, relapse patients have shown to be in complete remission for a long period. This therapy approach can be effective in removing metastatic cells in addition to treating local malignancies. Unlike the conventional adaptive immune cells, CAR-T cell treatment is a targeted therapy with great specificity that can eradicate cancer cells expressing the relevant tumor-associated antigens. As a result, this therapeutic strategy will prevent the unnecessary destruction of healthy normal cells to a large amount. CAR-T cells, surprisingly, can detect cell surface antigens without the need for MHC gene expression. By masking MHC or surface molecules involved in antigen processing and presentation, cancer cells cannot evade the immune system (T cell immune surveillance). It's worth noting that CAR-T cells are probably certainly capable of detecting a variety of antigens, including lipids, carbohydrates, and proteins. Furthermore, chimeric antigen receptors feature a flexible intracellular signaling domain that permits the cell to prevent tumor cells from directly or indirectly downregulating costimulatory molecules.
- Conclusion: Therefore, CAR T cell technology is indicated as a suitable candidate for ALL treatment as an immunotherapy-based method. As a result, this technique has a lot of promise in terms of cancer treatment. Although it faces significant obstacles such as cytotoxicity, cytokine release syndrome, neurotoxicity, and ICANS. After chemotherapy approaches fail, the development of different generations of CAR technology and its combined usage in other ways, such as hematopoietic stem cell transplantation, can be employed as an effective method of ALL treatment. Using alternate therapy strategies to address these issues appears to be critical. T cells genetically modified with Chimeric Antigen Receptor (CAR) treatment for ALL have been extensively investigated in the previous decade and represent a new era of strategy. According to the results of Phase I/II clinical trials, this technique appears to be very promising and could be employed as an effective and safe treatment for ALL soon.
- Keywords: CAR T-cell, Acute lymphoblastic leukemia, immunotherapy, clinical
