Chimeric antigen receptor T-cell therapy to target hematologic malignancies

Abstract

Several decades of humoral immunotherapy using monoclonal antibodies and cellular immunotherapy using hematopoietic cell transplantation have recently culminated in a successful merger: the development and clinical application of genetically engineered antibody-T cell chimeras. Also known as chimeric antigen receptor T cells (CAR T cells), these entities combine the exquisite antigen specificity of antibodies with the polyfunctionality and potency of cellular immunity and are a prime example of the potential for synthetic biology to treat disease. CAR T cells overcome several of the biologic obstacles that have historically hampered immunotherapy while providing fundamental mechanistic insights into cellular immunology and revealing new challenges in genetic engineering and target selection. Results from early-phase CAR T-cell-based clinical trials demonstrate the significant potential for this approach to affect dramatic and complete clinical responses while revealing novel toxicities associated with activation of potent and specific antitumor immunity.