B-lymphocyte antigen CD19 and Natural Killer cell activating receptor ligands (CD19/NKRL)

This target profile represents a dual-targeting approach used in advanced immunotherapies, specifically CAR-NK cells. It combines the B-lymphocyte antigen CD19, a 95 kDa transmembrane glycoprotein essential for B-cell signaling (UniProt P15391), with ligands for Natural Killer (NK) cell activating receptors. CD19 is a well-established target for treating B-cell malignancies like leukemia and lymphoma (PubMed 32023371). The second component of this target profile refers to stress ligands such as MICA, MICB, and ULBPs, which are upregulated on tumor cells and recognized by NK receptors like NKG2D (PubMed 32024998). This dual approach, exemplified by CAR-NK cell therapies like TAK-007, allows for the specific elimination of CD19-positive malignant B cells while simultaneously utilizing the NK cell's innate ability to destroy tumor cells that may have escaped CD19-targeted therapy through antigen loss or downregulation (Takeda, 2019). This strategy aims to overcome resistance mechanisms common in single-antigen targeted therapies. Clinical applications focus on relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia. Safety profiles for these therapies often show a lower incidence of severe cytokine release syndrome compared to traditional CAR-T cells.

Other names

CD19B4NKG2D ligandsMICAMICBULBPStress-induced ligands

Dual-mechanism cytotoxicity involving CAR-mediated targeting of CD19 and innate receptor-mediated recognition of stress ligands on tumor cells.