可变淋巴细胞受体 B 技术——是否已准备好进入主流应用？

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. Jawless vertebrates, such as lamprey, use Variable Lymphocyte Receptor B (VLRB) antibodies to recognize target antigens which work similarly to antibodies (Abs) in humans and other mammals. The unique architecture and evolutionary distance of VLRB antibodies allow them to bind to targets that mammalian Abs might not be able to recognize. The simple structure of VLRBs also allows for efficient genetic modification and production. Here, we review the current experience with VLRB technologies and discuss their potential benefits for clinical and research applications. VLRB-based technologies are currently being investigated for diagnosis, imaging, and treatment of diverse conditions, including solid organ and hematological malignancies, infections, autoimmunity, and degenerative and metabolic disorders. They can directly recognize disease biomarkers, such as B cells from chronic lymphocytic leukemia, deliver drugs to the brain, kill cancer cells, and create vaccines. The extensive knowledge gained with VLRB technologies emphasizes their promise for translation into clinical applications and readiness for prime time.