Chronic lymphocytic leukemia-associated antigens (CLL-associated antigens) (CLL-associated antigens)

Chronic lymphocytic leukemia (CLL)-associated antigens represent a collection of surface proteins that are characteristically expressed on the surface of malignant B-cells. This group includes well-known markers such as CD19, CD20, CD23, and CD5, as well as more specific targets like Receptor tyrosine kinase-like orphan receptor 1 (ROR1) and CD79b (Hallek et al., 2018; Daneshmanesh et al., 2008). These antigens are integral to the pathophysiology of CLL, participating in B-cell receptor (BCR) signaling pathways, mediating interactions with the lymphoid microenvironment, and promoting the survival and anti-apoptotic nature of the leukemic clones (Kipps et al., 2017). From a therapeutic perspective, these antigens serve as the primary docking sites for a wide array of immunotherapies, including monoclonal antibodies like rituximab and obinutuzumab, which induce cell death through complement activation and immune-mediated lysis (Goede et al., 2014). Additionally, novel modalities such as CAR-T cells and antibody-drug conjugates (ADCs) leverage these antigens to deliver potent cytotoxic payloads or direct T-cell activity specifically to the tumor (Neelapu et al., 2017). Despite their success, targeting these antigens can lead to significant side effects, most notably the depletion of healthy B-cells resulting in secondary immunodeficiency and the risk of cytokine release syndrome during intensive cellular therapies (Wierda et al., 2021).

Other names

CLL surface markersB-cell CLL antigensCLL-specific antigens

Monoclonal antibodies targeting these antigens primarily act through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Antibody-drug conjugates (ADCs) utilize these antigens for targeted internalization of cytotoxic payloads. Bispecific antibodies and CAR-T cells leverage these antigens to facilitate direct T-cell mediated lysis of the leukemic cells.