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B-lymphocyte antigen CD19 (UniProt P15391) and B-cell activating factor receptor (BAFF-R, UniProt Q96RJ3) are critical surface proteins expressed throughout B-cell development. CD19 functions as a dominant signaling component of the B-cell antigen receptor complex, while BAFF-R (also known as TNFRSF13C) is essential for the survival of mature B cells by mediating signals from the B-cell activating factor (BAFF) (PubMed: 11520416). In B-cell malignancies like Non-Hodgkin Lymphoma and Acute Lymphoblastic Leukemia, these receptors are frequently overexpressed, making them ideal therapeutic targets (PubMed: 31554742). While CD19-targeted therapies like Tisagenlecleucel have shown success, tumor relapse often occurs through CD19 antigen loss. Dual-targeting of CD19 and BAFF-R, particularly through bispecific CAR-T cell therapies, is designed to prevent this antigen escape by ensuring that the loss of one target does not result in immune evasion (ClinicalTrials.gov: NCT04020211). This combinatorial approach aims to provide more durable clinical responses in patients with refractory B-cell cancers.
Simultaneous or sequential binding to CD19 and BAFF-R antigens on malignant B-cell surfaces to induce T-cell mediated cytotoxicity and overcome resistance mediated by antigen loss.
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