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19z1 CAR T cells

Development stage
Preclinical
Lead developer
Memorial Sloan Kettering Cancer Center
Modality
CAR-T Cells → Engineered T Cells → Adoptive Cell Transfer → Cell Therapies
Administration
Intravenous
01

Overview

19z1 CAR T cells are a **first-generation chimeric antigen receptor T cell therapy** targeting CD19, developed as one of the earliest prototypes of CAR T cells for B cell malignancy. The CAR consists of a single-chain variable fragment (scFv) specific for human CD19 (derived from the SJ25C1 hybridoma), fused to the hinge and transmembrane domain of human CD8α, and a cytoplasmic CD3ζ signaling domain. Unlike later CAR T cell generations, 19z1 does not include additional costimulatory domains (such as CD28 or 4-1BB) and thus relies primarily on the CD3ζ-mediated T cell activation signal. These cells were originally tested for the treatment of human B cell malignancies, including Burkitt lymphoma and B-acute lymphoblastic leukemia, both in vitro and in xenograft mouse models. 19z1 CAR T cells demonstrated **antigen-specific killing** of CD19+ malignant B cells, but their persistence and expansion in vivo were limited without supplemental costimulation. Preclinical studies showed improved outcomes with adjunct therapies like costimulatory molecule expression on artificial antigen-presenting cells or cyclophosphamide preconditioning. 19z1 is mainly of historical and research relevance as a forerunner to second- and third-generation CAR T cell therapies that incorporate costimulatory domains for enhanced efficacy and persistence[1][3].

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