Variable Lymphocyte Receptor B Technologies – Are They Ready for Prime Time?

To review the current and the potential research and clinical use of VLRBs. A literature search was conducted for English studies published in the past 20 years using the terms "Variable Lymphocyte Receptor," "VLR," "VLRB" or "Repebody." Only primary reports were included. VLRB-based technologies are currently being investigated for diagnosis, imaging, and treatment of diverse conditions including solid organ and hematological malignancies, infectious diseases, autoimmunity, and degenerative and metabolic disorders. VLRB mAbs can be used to directly recognize disease biomarkers, such as B cells from chronic lymphocytic leukemia, or to deliver drugs to the brain or cancer cells. The VLRB C-terminal multimerization domain has been utilized to create vaccines while VLR-based chimeric antigen receptor (CAR) T cell constructs are being investigated for cancer therapies. The extensive knowledge gained with VLRB mAbs in diverse in vitro and in vivo models emphasizes their promise for translation into clinical applications and readiness for prime time.