Gene-knocked out chimeric antigen receptor (CAR) T cells: Tuning up for the next generation cancer immunotherapy

Recently clinical trials utilizing genetically engineered T cells expressing a chimeric antigen receptor (CAR) that is half monoclonal antibody and half T-cell receptor have demonstrated remarkable response in patients with advanced cancers like relapsed or refractory acute lymphoblastic leukemia (ALL) and lymphoma. Moreover, emerging chimeric genome editing tools such as zinc-finger nucleases (ZNFs), transcription activator-like effector nucleases (TALENs) and clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas composed of sequence-specific DNA binding module(s) linked to a non-specific DNA cleavage domain have made possible to dramatically expand the ability to manipulate cells aim to treat and/or study a wide range of diseases including cancer. Here, we will discuss how joint application of these two chimeras will help us to manipulate CAR T cells aiming to enhance the efficacy of CAR T cell therapy in preclinical and clinical settings.