AUTHOR=Dwivedi Alka , Karulkar Atharva , Ghosh Sarbari , Rafiq Afrin , Purwar Rahul TITLE=Lymphocytes in Cellular Therapy: Functional Regulation of CAR T Cells JOURNAL=Frontiers in Immunology VOLUME=9 YEAR=2019 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.03180 DOI=10.3389/fimmu.2018.03180 ISSN=1664-3224 ABSTRACT=

Lymphocytes especially autologous T cells have been used for the treatment of numerous indications including cancers, autoimmune disorders and infectious diseases. Very recently, FDA approved Chimeric Antigen Receptor T cells (CAR T cells) therapy for relapse and refractory CD19+ B cell acute lymphoblastic leukemia (r/r B-ALL) and r/r diffuse large B cell lymphoma (r/r DLBCL) upon their remarkable success in multiple Phase I-II clinical trials. While CAR T cells are considered as major breakthrough in the field of cancer immunotherapy, the regulation of CAR T cells remains poorly understood. In this review we will discuss the strategies that regulate the CAR T cells efficacy and persistence with focus on roles of different structural component of CAR construct. Different domains of CAR construct, for example, antigen binding domain, hinge, transmembrane, and signaling domain as well as immune-regulatory cytokines have significant impact on CAR T cell efficacy. Finally, this review will highlight the strategies that will promote CAR T cells efficacy and will reduce the toxicity.