A Novel Carbohydrate Antibody to GalNac1-3Gal and Its Application for Cancer Diagnostic and Prognosis

Cervical cancer is one of the most common cancers among women worldwide. Currently, physical descriptors such as tumor size and depth are the primary factors used for deciding the course of treatment. Despite significant efforts to identify prognostic biochemical markers or therapeutic targets to improve diagnosis and treatment, none have achieved routine clinical use. An example of one previously identified biomarker is the Tn antigen, a carbohydrate moiety composed of a GalNAc residue linked to serine or threonine. Previous studies examining Tn antigen levels present in cervical cancer tumors have produced conflicting results. The inventors discovered that this phenomenon is a direct result of using antibodies that are cross reactive to carbohydrates terminating in GalNAcal-3Gal or GalNAca1-6Gal. To precisely determine which carbohydrate antigen correlates with cervical cancer formation, the investigators produced a series of antibodies with high degrees of specificity for structurally distinct variants of the Tn antigen. The results show that relative to other carbohydrate antigens examined, GalNAca1-3Gal is expressed at high levels in squamous carcinomas of the cervix.  Importantly, expression levels of GalNAcal-3Gal have a statistically significant correlation with 5-year survival rates. 

Researchers at NCI developed antibodies with high specificity for GalNAca1-3Gal, which can be used to both diagnose cervical cancer and as a prognostic tool. In addition to cervical cancer, elevated GalNAc1-3Gal is present in a variety of other human carcinomas, including squamous cell carcinoma, esophageal cancer, laryngeal cancer, and skin cancer.