Sialyl Lewis-a carbohydrate antigen (sLeA)

Sialyl Lewis-a (sLeA), also known as Carbohydrate Antigen 19-9 (CA19-9), is a tetrasaccharide tumor-associated carbohydrate antigen (TACA) that is highly expressed on the surface of various adenocarcinomas, including pancreatic, colorectal, and gastric cancers [1.2.1, 1.3.1]. It functions as a high-affinity ligand for E-selectin, an adhesion molecule expressed on vascular endothelial cells, which facilitates the extravasation and hematogenous metastasis of circulating tumor cells [1.1.2, 1.1.4]. Beyond its role in cell adhesion, sLeA is involved in immune evasion by interacting with sialic acid-binding immunoglobulin-like lectins (Siglecs) on immune cells [1.1.2, 1.3.3]. Clinically, CA19-9 is the most widely used serum biomarker for monitoring disease progression and treatment response in pancreatic cancer [1.2.3, 1.3.2]. Therapeutic development targeting sLeA includes monoclonal antibodies like MVT-5873 (HuMab-5B1) and antibody-drug conjugates like gancotamab, which aim to induce immune-mediated tumor destruction or block metastatic pathways [1.3.4, 1.4.2]. However, its utility is limited in the 5-10% of the population who are Lewis-negative and cannot synthesize the antigen, leading to potential false-negative diagnostic results [1.2.2, 1.2.3]. Additionally, elevated levels can be observed in benign conditions such as pancreatitis or obstructive jaundice, complicating its use as a standalone diagnostic tool [1.2.2, 1.4.1]. Recent research also suggests that sLeA expression may play a causative role in the development of pancreatitis by hyperactivating EGFR signaling [1.2.1, 1.3.2].

Other names

CA19-9Cancer antigen 19-9Sialyl Lewis AsLe^aSialyl-Lewis ACarbohydrate antigen 19-9

Monoclonal antibodies targeting sLeA mediate tumor cell killing through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), and can also inhibit metastasis by blocking the interaction between sLeA and E-selectin on endothelial cells [1.3.1, 1.4.2].