Unlocking the potential of melanotransferrin (CD228): implications for targeted drug development and novel therapeutic avenues.

Introduction: Melanotransferrin (CD228), a cell membrane-anchored protein, has emerged as a significant cancer antigen due to its high expression in various solid tumors. This review synthesizes the current understanding and therapeutic potential of CD228.

Areas covered: We conducted a literature search using PubMed, Web of Science, and ClinicalTrials.gov with the keywords 'melanotransferrin' and 'CD228.' Our comprehensive review examines CD228 and its isoforms, membrane-bound CD228 (mMFI2) and soluble CD228 (sMFI2), their roles in tumorigenesis, angiogenesis, endothelial cell migration, plasminogen activation, and transendothelial transport across the BBB, as well as the current state of drug development efforts targeting CD228.

Expert opinion: Targeting CD228 represents a promising therapeutic strategy in oncology, with mMFI2 as a potential target for solid tumors and sMFI2 valuable for disease diagnosis in malignant tumors, Alzheimer's disease, and arthritis, and facilitating macromolecular drug delivery across the blood-brain barrier (BBB). Despite its potential to transform the treatment landscape for numerous solid cancers, further research into the precise mechanisms and clinical translation of CD228-directed treatments is needed to maximize its therapeutic utility.