B-lymphocyte antigen CD19 (truncated) (CD19t)

B-lymphocyte antigen CD19 (truncated), or CD19t, is a modified cell-surface protein derived from the native CD19 molecule, featuring the extracellular and transmembrane domains but lacking the intracellular signaling tail. In this therapeutic context, CD19t is utilized as a synthetic target to expand the utility of CD19-directed CAR-T cell therapies—originally designed for B-cell malignancies—into the realm of solid tumors. Because solid tumors often lack uniform, highly specific targets, researchers use delivery systems like oncolytic viruses (e.g., OV19t) to selectively infect tumor cells and force them to display the CD19t antigen on their surface (Park et al., 2020, Science Translational Medicine; City of Hope, 2020). Once the tumor cells are labeled with CD19t, they become susceptible to recognition and destruction by FDA-approved CD19 CAR-T cells, such as Tisagenlecleucel or Axicabtagene ciloleucel. This approach effectively turns the solid tumor into a target that the immune system is already primed to attack using existing cellular therapies. Clinical development of this strategy is ongoing, focusing on safety and the efficiency of antigen delivery to ensure robust T-cell recruitment and tumor eradication while minimizing off-target effects in healthy tissues (ClinicalTrials.gov, NCT04381741).

Other names

Truncated CD19tCD19CD19 extracellular domainCD19 ECDCD19-delta-cytoplasmic domain

The truncated CD19 (CD19t) protein is delivered to and expressed on the surface of non-B-cell tumor cells (typically solid tumors) via a delivery vector such as an oncolytic virus. Once expressed, the extracellular domain of CD19t serves as a synthetic target for CD19-specific chimeric antigen receptor (CAR) T-cells. The CAR-T cells bind to the CD19t antigen, triggering T-cell activation, secretion of cytotoxic granules (perforin and granzyme), and subsequent lysis of the tumor cell (Park et al., 2020, Science Translational Medicine).