Lewis a-like carbohydrate antigen (AG-7)

The Lewis a-like carbohydrate antigen, also known as the AG-7 antigen, is a tumor-associated carbohydrate antigen (TACA) that is frequently overexpressed in various gastrointestinal malignancies, including gastric, pancreatic, colorectal, and biliary cancers. It is a glycol-epitope related to the Lewis blood group system, characterized by its presence on the surface of cancer cells in approximately 24% to 61% of patients. In normal tissues, its expression is highly restricted, primarily found on the luminal surfaces of the gastrointestinal epithelium and secretory glands, which provides a therapeutic window for targeted intervention. The antigen serves as a target for novel immunotherapies, most notably the antibody-drug conjugate (ADC) AbGn-107, which consists of a humanized monoclonal antibody (AbGn-7) linked to a potent cytotoxic payload. Upon binding to the Lewis a-like carbohydrate, the ADC is internalized via the lysosomal pathway, releasing the drug to induce cell death. Clinical trials have evaluated these agents in heavily pretreated patients, showing modest efficacy and a safety profile characterized by manageable toxicities such as neutropenia and fatigue. The antigen's role in cancer is primarily as a marker of aberrant glycosylation, which can facilitate tumor progression and immune evasion. Targeting this carbohydrate moiety represents a shift from traditional protein-based targets, leveraging the unique glycan signatures of malignant cells.

Other names

AG-7 antigenAbGn-7 antigenLewis a-like glycotopeLewis a-like glycol-epitope

Antibody-drug conjugate (ADC) mediated delivery of cytotoxic payloads; Antibody-dependent cellular cytotoxicity (ADCC); Complement-dependent cytotoxicity (CDC)