B-lymphocyte antigen CD19 (truncated extracellular domain) (CD19t)

The truncated extracellular domain of B-lymphocyte antigen CD19 (CD19t) is a synthetic cell-surface antigen used to redirect CD19-specific chimeric antigen receptor (CAR) T cell therapies toward solid tumors. Naturally, CD19 is a 95 kDa type I transmembrane glycoprotein expressed exclusively on B cells and is a critical co-receptor for B-cell antigen receptor signaling (UniProt P15391). In this therapeutic context, a truncated version of CD19—retaining the extracellular epitope but lacking the intracellular signaling domain—is delivered to tumor cells via an engineered oncolytic virus, such as the chimeric orthopoxvirus CF33-CD19t (Priceman et al., Sci Transl Med, 2020). Once the virus infects the tumor cells, they begin to express CD19t on their surface, effectively tagging them for recognition and destruction by CD19-directed CAR-T cells, such as Axicabtagene ciloleucel or Tisagenlecleucel. This approach, often referred to as the Oncolytic Virus-delivered CD19 or OV19t strategy, aims to overcome the challenges of antigen heterogeneity and the immunosuppressive microenvironment in solid tumors like triple-negative breast cancer and glioblastoma (NCT04381741). By converting the tumor into a CD19-positive target, this strategy leverages the high potency of existing B-cell-directed immunotherapies for non-B-cell malignancies.

Other names

CD19-tCD19Δcyttruncated CD19CD19-truncated extracellular domain

Oncolytic virus-mediated delivery of a truncated CD19 transgene to tumor cells, followed by CAR-T cell recognition and lysis of CD19t-expressing cells (Priceman et al., Sci Transl Med, 2020).