CD99 antibody targets the CD99 antigen, a cell surface glycoprotein encoded by the *MIC2* gene located in the pseudoautosomal region of the X and Y chromosomes. First identified in the 1980s, CD99 is highly expressed in various cell types, including T lymphocytes, endothelial cells, and certain epithelial and mesenchymal tissues. It plays roles in cell adhesion, migration, apoptosis, and transmembrane signaling, though its exact biological functions remain partially understood. Structurally, CD99 contains a conserved extracellular domain critical for homophilic interactions and intracellular signaling.
In diagnostic pathology, CD99 antibodies are widely used as immunohistochemical markers. They are particularly valuable in distinguishing Ewing sarcoma (ES) and primitive neuroectodermal tumors (PNETs), which show strong membranous CD99 expression, from other small round blue cell tumors. However, CD99 is not entirely specific, as it is also expressed in lymphoblastic lymphomas, synovial sarcomas, and some carcinomas.
Therapeutically, CD99 has gained attention as a potential target in oncology. Anti-CD99 antibodies have shown preclinical efficacy in inducing apoptosis or inhibiting proliferation in T-cell acute lymphoblastic leukemia (T-ALL) and osteosarcoma models. Recent studies explore antibody-drug conjugates (ADCs) or bispecific antibodies leveraging CD99’s surface expression. Despite progress, challenges remain, including understanding CD99’s dual roles in pro-oncogenic and tumor-suppressive contexts and optimizing targeted therapies for clinical translation. Ongoing research aims to clarify its signaling mechanisms and expand its diagnostic and therapeutic applications.