B-lymphocyte antigen CD19 (truncated) expressed by oncolytic virus CF33 (CF33-hCD19t)

The CD19 epitope displayed on CF33-hCD19t-infected tumor cells refers to a truncated version of the human B-lymphocyte antigen CD19 (hCD19t) that is delivered to and expressed on the surface of solid tumor cells via an engineered chimeric orthopoxvirus (CF33). This therapeutic strategy, often called 'OncoCAR,' is designed to overcome the lack of lineage-specific targets in solid tumors by forcing the tumor to express a well-validated B-cell antigen (Park et al., 2020). The hCD19t protein is specifically engineered to lack the intracellular signaling domain, ensuring it cannot initiate endogenous B-cell signaling within the tumor cell while retaining the extracellular epitopes required for recognition by CD19-directed therapies (City of Hope, 2020). By utilizing the CF33 virus as a delivery vehicle, the treatment induces de novo antigen expression specifically within the tumor microenvironment, effectively 'flagging' the tumor for destruction by the immune system. Once the tumor cells express hCD19t, they become susceptible to potent killing by CD19-specific chimeric antigen receptor (CAR) T cells or bispecific T-cell engagers (BiTEs) like blinatumomab (O'Leary et al., 2022). This approach combines the direct oncolytic activity of the virus—which lyses tumor cells and releases tumor-associated antigens—with the high specificity and cytotoxicity of CAR-T cell therapy, potentially turning 'cold' tumors 'hot' and improving therapeutic outcomes in various solid malignancies.

Other names

hCD19tTruncated human CD19CF33-CD19OncoCAR-19 targetCD19t

The target functions as an artificial cell-surface marker; the CF33 oncolytic virus infects solid tumor cells and forces them to express a truncated human CD19 (hCD19t) protein, which then serves as a target for CD19-specific chimeric antigen receptor (CAR) T cells to recognize and eliminate the tumor cells (Park et al., 2020).