Prominin-1 (PROM1) (PROM1)

Prominin-1 (PROM1), widely known as CD133, is a pentaspan transmembrane glycoprotein that localizes to membrane protrusions such as microvilli and cilia (UniProt: P29323). The AC133 epitope is a specific glycosylation-dependent region of the PROM1 protein that is highly expressed on the surface of hematopoietic stem cells and various cancer stem cells (PubMed: 9354819). In oncology, CD133 is a critical marker for identifying and targeting the subpopulation of cells responsible for tumor initiation, progression, and chemoresistance in cancers such as glioblastoma and colorectal carcinoma (PubMed: 17167416). Therapeutic strategies targeting the AC133 epitope include CAR-T cell therapies, such as CART-133, and antibody-drug conjugates designed to selectively eradicate these cancer stem cells (ClinicalTrials.gov: NCT02541370). Beyond its role in cancer, mutations in the PROM1 gene are associated with various forms of retinal degeneration, including Stargardt disease and macular dystrophy (PubMed: 18326624). However, the use of CD133 as a therapeutic target is complicated by its expression on healthy hematopoietic stem cells and endothelial progenitor cells, which poses a risk for on-target off-tumor toxicity (PubMed: 24652995).

Other names

CD133AC133 antigenAntigen AC133Pentaspan-1MCDR2STGD4CORD12RP41

Targeted elimination of cancer stem cells (CSCs) through the recognition of the AC133 glycosylation-dependent epitope by Chimeric Antigen Receptor (CAR) T-cells or Antibody-Drug Conjugates (ADCs), leading to direct cell lysis or delivery of cytotoxic payloads (PubMed: 24652995, ClinicalTrials.gov: NCT02541370).