High Affinity Monoclonal Antibodies Targeting Glypican-1

Pancreatic cancer is the fourth most common cause of death from cancer in the U.S. The overall 5-year survival rate for this disease is 8.5%. Glypican-1 (GPC1), a cell surface heparan sulfate proteoglycan protein that is overexpressed in pancreatic cancer. Due to this preferential expression, GPC1 represents a potential candidate for targeted therapy for patients with pancreatic cancer and other GPC1 expressing cancers such as prostate cancer.

Researchers at the National Cancer Institute’s (NCI) Laboratory of Molecular Biology have developed and isolated two new antibodies that target GPC1 (HM2 and D4). These new antibodies have been shown to specifically target GPC1-expressing cell lines. These GPC1 antibodies can be used as either independent agents or targeting domains in immunoconjugates such as recombinant immunotoxins (RITs), antibody-drug conjugates (ADCs), chimeric antigen receptors (CARs), bispecific antibodies, etc. Significantly, CARs using these antibodies have shown specific killing activity against GPC1 positive tumors – including GPC1 expressing cell and mouse models. Such data strongly support that these candidates may be further developed as therapeutics. 

Competitive Advantages:

• New HM2 and D4 antibodies with high GPC1 binding specificity will result in less non-specific cell killing and lower potential side-effects
• There is a first to market potential because there are no known clinical trials using GPC1-targeted therapies

Commercial Applications:

• Therapeutic applications include the unconjugated antibodies and their use as a targeting moiety for CARs, RITs, ADCs, and bispecific antibodies
• Potential therapeutic benefit for several cancer types with few treatment options – including uterine cervical cancer and pancreatic adenocarcinoma
• Diagnostic agent for detection and monitoring levels of GPC1-expressing cancers