Introduction: Chimeric antigen receptor T-cell therapy (CAR T-cell) offers a new treatment option for patients with diffuse large B-cell lymphomas and acute lymphoblastic leukemia (ALL), both aggressive forms of blood cancer. CAR T cells are patient-modified T cells that are genetically engineered to target a cancerous cell's surface antigen with their synthetic receptors, which reprogram T cells to fight cancer. In this way, the immune system targets cancerous cells and increases the effectiveness of cancer therapies. The CAR is the central component of CAR-T cells, forming T cells major histocompatibility complex (MHC) unrestricted. Modified T cells can recognize a broader range of targets than natural TCR molecules on T cell surfaces. CARs are recombinant receptors that can bind to tumor antigens and activate T cells at the same time. The CAR consists of three distinct parts, each with a different task. An extracellular domain is a single-chain variable antibody domain (scFv), that is able to recognize specific antigens of tumors. A small segment of polypeptide connects the heavy-chain variable region (VH) to the light-chain variable region (VL) of antibodies. The scFv on CAR-T cells allows them to recognize and bind directly to tumor-specific antigens. The hinge domain consists of members of the immunoglobulin superfamily, such as CD8, CD28, or IgG, which are involved in signal transduction. Signal transduction within the intracellular space is primarily due to the TCR CD3ζ chain. CAR-T cells identify tumor surfaces antigens directly and they are not limited by MHC class. In response to this binding, CAR-T cells multiply and destroy tumor cells. Initially, CAR T cells have been used to treat malignancies that express the CD19 antigen, such as lymphoma and ALL. Moreover, CAR T cells can target other targets, including overexpressed antigens, such as epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), glycosylated abnormal proteins such as mucin 1 (MUC1), oncofetal antigens such as carcinoembryonic antigen (CEA), tumor-associated stromal proteins such as fibroblast activating protein (FAP) and immune-modulating antigens such as program death-ligand 1 (PD-L1). TCR-T cells can recognize any antigen presented by MHC molecules, whether they are intracellular or surface antigens or neoantigens produced by tumor cells after mutation, and also TCR can recognize the internal molecules of cancer cells. When a small amount of antigen is present, TCR-T cells can be fully activated because they retain all the auxiliary molecules of the TCR signal transduction pathway. There are several side effects associated with CAR T cells that are related to the way they attack cancer cells in All patients. Often, patients suffer from cytokine release syndrome (CRS) due to excessive T-cell activation. Symptoms of CRS can include high fever, hypotension, hypoxia, and even organ failure. Inflammatory cytokines such as IL-6, IFNγ, and TNFα are responsible for these symptoms. A longer-term side effect can also happen due to the normal expression of the CD19 protein on normal B cells, which are a type of white blood cell that functions as part of the immune system by releasing antibodies. As a result of the treatment, patients can have low levels of antibody production and become more susceptible to infection.
Methods: CAR T-cell therapy involves genetically editing a patient's T-cells to express a CAR that recognizes an antigen-specific to his or her tumor, followed by ex vivo cell expansion and re-infusion back into the patient. T-cell genetic modification may take place either via viral-based gene transfer methods or nonviral methods.
Results: A genetically manipulated CAR T cell can target specific cancer cells; it has been successfully used in research facilities to treat solid and suspended cancers. This method uses the patient's own peripheral blood mononuclear cells and after some special experiments, these modified T cells can recognize and bind to specific antigens on cancer cells and destroy them.
Conclusion: It has been shown that CAR-T cells are an effective and promising treatment for cancer but they also faced many challenges. The CAR-T cell therapy is simply the beginning of immunotherapy, not the end. In addition, future treatment schemes must combine immunotherapy with other methods.