CAR-T cell therapy for B-cell lymphoma

Non-Hodgkins B-cell lymphoma (NHL) comprises highly aggressive(ex. High grade B-cell lymphoma), aggressive (ex.Diffuse large B-cell lymphoma) and indolent disease. Chromosomaltranslocation has an important role in pathogenesisof many types of B-cell lymphoma. According to the reportsof the patients taking different therapeutic methods for curingB-cell lymphoma, FDA was approved Chimeric antigen receptor-modified (CAR) T-cell therapy for a variety of lymphomasubtypes. In this therapeutic method, the CAR structure is engineeredin a way that it works optimally in relation to the levelof tumor antigen expressed on malignant cells, tumor burdenand else .Chimeric antigen receptors (CARs) are receptors with multiplecomponents: a) an antigen-binding domain derived from monoclonalantibodies that must have high affinity without toxicityb) The hinge region affects CAR function, expression, signaling,and epitope recognition c) The transmembrane domainconnects CAR to the T cell membrane and affects its expressionand signaling. To achieve effective therapeutic responses, a CAR-T cell antigen-binding domain must bind its target epitopeand reach a minimum threshold level to induce CAR-T cell activationand cytokine secretion. Cytokine secretion by activatedCAR-T cells can also be modulated by modifying the hinge andtransmembrane regions. An attractive strategy to solve the challengeof poor T-cell proliferation and short-term T-cell persistenceinvolves engineering CAR-T cells to deliver stimulatoryimmune signals in the form of stimulatory cytokines that enhanceT-cell survival, proliferation, and antitumor activity andbalances the tumor microenvironment.B-cell lymphomas almost express the CD۱۹ protein on theircell surface. CD۱۹ is a transmembrane glycoprotein that playsa role in regulating B cell activation in an antigen receptor-dependentmanner and is uniformly expressed in all stages of Bcell differentiation. Therefore, the use of CD۱۹-directed CARtherapy has been the subject of intense research for B-cell non-Hodgkin's lymphomas (NHL).

کلیدواژه ها:

CAR-T Cell Therapy ، B-cell lymphoma ، TargetedTherapy ، Blood Cancer ، Immunotherapy