Overcoming Cd19 Antigen Loss In B-Cell Malignancies With Car T Cells Targeting Baff-R

Background: The current success in treating hematological malignancies with CD19 targeted chimeric antigen receptor (CAR) T cells is diminished by tumor relapse from target antigen loss. The B-cell activating factor-receptor (BAFF-R), a tumor necrosis factor receptor superfamily protein (TNFRSF13C), is a particularly interesting alternative target in CD19 relapsed disease and in B cell malignancies in general. BAFF-R null mice exhibit greatly reduced normal B-cell numbers and mouse strains expressing a mutant BAFF-R exhibited decreased B-cell life spans and a dramatically reduced peripheral B-cell compartment. Thus, BAFF-R signaling is a driver of B-cell survival, which may limit the capacity of clonal B-cell tumors to escape therapy by down-regulation of antigen expression.