Truncated B-lymphocyte antigen CD19 (CD19t)

Truncated B-lymphocyte antigen CD19 (CD19t) is a modified, non-signaling version of the CD19 protein engineered to be expressed on the surface of tumor cells that do not naturally possess the antigen, such as solid tumors [1]. This target is typically introduced into the tumor microenvironment via a delivery vehicle, most notably an oncolytic virus (e.g., OV-CD19t), which infects cancer cells and forces them to produce and display the CD19t protein on their cell membranes [1][2]. Once expressed, CD19t acts as a synthetic neo-antigen or docking site for anti-CD19 chimeric antigen receptor (CAR) T cells, which are otherwise unable to recognize solid tumor cells due to the lack of suitable endogenous targets [1][3]. This mark and kill strategy leverages the high potency and established clinical success of CD19-directed CAR-T therapies, originally developed for B-cell malignancies, and applies them to a broader range of cancers [2]. The truncation of the CD19 molecule is critical as it removes the intracellular signaling domain, preventing the protein from initiating any B-cell receptor-like signaling within the tumor cell while maintaining the extracellular epitope required for CAR-T recognition [1]. Clinical applications of this target are currently being explored in various solid tumors, including triple-negative breast cancer and glioma, where antigen heterogeneity often limits the efficacy of traditional targeted therapies [3]. Sources: [1] Park, A. K., et al. (2020). Effective combination immunotherapy using oncolytic viruses to deliver CAR targets to solid tumors. Science Translational Medicine, 12(559). doi: 10.1126/scitranslmed.aaz1863. [2] City of Hope. (2020). City of Hope Researchers Develop Oncolytic Virus to Deliver CAR T Cell Targets to Solid Tumors. [3] ClinicalTrials.gov. (2020). Oncolytic Virus (OV19t) and CD19 CAR T Cells for the Treatment of HER2-Negative Solid Tumors. Identifier: NCT04381741.

Other names

CD19tTruncated CD19CD19-delta-cytoplasmicOncolytic virus-delivered CD19tSynthetic CD19 neo-antigen

The target (CD19t) is expressed on the surface of tumor cells via a delivery vector (e.g., oncolytic virus), serving as a synthetic docking site for anti-CD19 CAR-T cells to induce tumor cell lysis [1][3].