Lewis Y antigen (CD174) (LeY)

Lewis Y (LeY) is a difucosylated tetrasaccharide (Fucα1-2Galβ1-4[Fucα1-3]GlcNAc) that functions as a tumor-associated carbohydrate antigen (TACA) and is classified as CD174 (Source: UniProt). In normal physiology, LeY expression is largely restricted to the secretory epithelia and the deep layers of the epidermis, but it is dramatically upregulated in over 70% of epithelial-derived carcinomas, including breast, colon, lung, and ovarian cancers (Source: PubMed PMID: 12683943). This overexpression is often associated with poor prognosis and increased metastatic potential, as the antigen plays a role in cell adhesion and signaling pathways that promote tumor progression. Because of its high density on tumor surfaces and limited distribution in normal tissues, Lewis Y has been extensively investigated as a target for various immunotherapeutic modalities. These include monoclonal antibodies like Hu3S193 and IGN311, which trigger immune effector functions such as antibody-dependent cellular cytotoxicity (ADCC). Furthermore, Lewis Y-targeted antibody-drug conjugates (ADCs) and chimeric antigen receptor (CAR) T-cell therapies are being developed to provide more potent anti-tumor responses (Source: PubMed PMID: 29439115). Despite its promise, challenges remain regarding the potential for 'off-tumor' toxicity due to low-level expression in some healthy tissues, necessitating careful patient selection and dose optimization.

Other names

LeYCD174Lewis Y blood group antigenDifucosyl-para-lacto-N-hexaose II

Drugs targeting Lewis Y primarily function through immune-mediated mechanisms, including antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) (Source: PubMed PMID: 15585918). Antibody-drug conjugates (ADCs) utilize the antigen for targeted delivery of cytotoxic agents like doxorubicin, while CAR-T cell therapies involve the genetic modification of T cells to express receptors that directly recognize and kill LeY-positive tumor cells (Source: ClinicalTrials.gov NCT03851146).