Signal transducer CD24 (neo-epitope) (neoCD24)

The neoCD24 epitope is a tumor-specific antigenic determinant found on the Signal transducer CD24 protein, a small glycosylphosphatidylinositol (GPI)-anchored sialoglycoprotein. While wild-type CD24 is expressed on various normal cells, including B cells and neutrophils, the neoCD24 epitope is selectively exposed on cancer cells due to aberrant glycosylation that otherwise shields the epitope in healthy tissues [1, 2]. CD24 functions as a critical "don't eat me" immune checkpoint by binding to Sialic acid-binding immunoglobulin-like lectin 10 (Siglec-10) on macrophages, thereby inhibiting phagocytosis and promoting immune evasion [1]. This epitope is highly prevalent across approximately 70% of human cancers, including hepatocellular carcinoma, breast, and ovarian cancers [2]. Therapeutic strategies targeting neoCD24, such as the monoclonal antibody ONC-781 and the bispecific T-cell engager ONC-783, aim to disrupt this inhibitory signaling and redirect the immune system to eliminate tumor cells [1, 2]. By specifically targeting the neo-epitope, these therapies seek to maximize anti-tumor efficacy while minimizing on-target, off-tumor toxicity associated with normal CD24 expression [1].

Other names

NeoCD24Tumor-specific CD24 epitopeCancer-specific CD24 epitopeCD24 neo-epitope

The neoCD24 epitope is targeted by monoclonal antibodies, bispecific T-cell engagers (BiTEs), and antibody-drug conjugates (ADCs) to disrupt the "don't eat me" signal mediated by the CD24/Siglec-10 interaction, thereby promoting macrophage-mediated phagocytosis and T-cell-mediated destruction of tumor cells.