The long road to the first FDA-approved gene therapy: chimeric antigen receptor T cells targeting CD19

Thirty years after initial publications of the concept of a chimeric antigen receptor (CAR), the U.S. Food and Drug Administration (FDA) approved the first anti-CD19 CAR T-cell therapy. Unlike other immunotherapies, such as immune checkpoint inhibitors and bispecific antibodies, CAR T cells are unique as they are "living drugs," that is, gene-edited killer cells that can recognize and kill cancer. During these 30 years of development, the CAR construct, T-cell manufacturing process, and clinical patient management have gone through rounds of failures and successes that drove continuous improvement. Tisagenlecleucel was the first gene therapy to receive approval from the FDA for any indication. The initial approval was for relapsed or refractory (r/r) pediatric and young-adult B-cell acute lymphoblastic leukemia in August 2017 and in May 2018 for adult r/r diffuse large B-cell lymphoma. Here we review the preclinical and clinical development of what began as CART19 at the University of Pennsylvania and later developed into tisagenlecleucel.

Indexed on Europe PMC as PubMed record 32014447 (DOI 10.1016/j.jcyt.2019.12.004). Its title names CD19 and its text names Diffuse large B-cell lymphoma; PubMed types it as a review (Research Support, Non-U.S. Gov't, research-article, Review, Research Support, N.I.H., Extramural). It was matched automatically to the idea "In vivo CAR-T as a vial on the shelf: a cost and access trial in lymphoma" and no figure has been checked by an editor.