Signal transducer CD24 (Tumor-associated neo-epitope) (NeoCD24)

The tumor-associated CD24 neo-epitope (NeoCD24) is a cancer-specific variant of the CD24 protein, a small, heavily glycosylated glycosylphosphatidylinositol (GPI)-anchored sialoglycoprotein [Drug Target Review, OncoC4]. While CD24 is widely expressed in normal tissues, the NeoCD24 epitope is uniquely exposed on the surface of various cancer cells—including breast, ovarian, and pancreatic cancers—while remaining shielded by glycans in healthy cells [OncoC4, Signal Transduction and Targeted Therapy]. This epitope serves as a critical component of the CD24/Siglec-10 'don't eat me' signaling axis, which allows tumor cells to evade the innate immune system by inhibiting macrophage-mediated phagocytosis [Nature, Frontiers in Immunology]. CD24 expression is also associated with cancer stem cell (CSC) properties, promoting tumor growth, metastasis, and resistance to therapy [Frontiers in Oncology, NIH]. Therapeutic strategies targeting NeoCD24, such as the monoclonal antibody ONC-781 and its derivatives (including CAR-T cells, bispecific antibodies, and antibody-drug conjugates), aim to disrupt this immune checkpoint [OncoC4, BMJ]. By specifically binding to the exposed neo-epitope on malignant cells, these therapies promote immune-mediated clearance of the tumor while minimizing off-target effects on normal tissues [Drug Target Review, OncoC4]. Clinical and preclinical studies are currently evaluating these modalities for their potential to treat both solid tumors and hematological malignancies [OncoC4, ResearchGate].

Other names

NeoCD24Neo-CD24Cancer-specific CD24 epitopeTumor-specific CD24 glycoformCD24 neoepitopeSignal transducer CD24

Blockade of the CD24-Siglec-10 interaction to enhance macrophage-mediated phagocytosis (ADCP) and NK cell-mediated cytotoxicity; induction of antibody-dependent cellular cytotoxicity (ADCC); and redirection of T cells or delivery of cytotoxic payloads via CAR-T, bispecific antibodies, or antibody-drug conjugates [Nature, OncoC4, BMJ].