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High Affinity Monoclonal Antibodies Targeting Glypican-1

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Researchers at the National Cancer Institute (NCI) have isolated two Glypican-1- (GPC1)- specific antibodies: the mouse monoclonal antibody HM2 that binds the C-lobe of GPC1 close to the cell surface, and the camel single domain antibody D4. The D4 single domain antibody (also called ‘nanobody’) has a high affinity for GPC1-positive tumor cells from both human and mouse origins. The NCI seeks licensing and/or co-development research collaborations to advance the development and commercialization of these antibodies.
NIH Reference Number
Product Type
  • Glypican-1, GPC1, Immunotoxin, Recombinant Immunotoxin, RIT, Chimeric Antigen Receptor, CAR, Antibody-drug Conjugate, ADC, Pancreatic Cancer, Single Domain Antibody, Nanobody, Bispecific Antibody, Ho
Collaboration Opportunity
This invention is available for licensing and co-development.
Description of Technology

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. 

Potential 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
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

Mitchell Ho Ph.D. (NCI), Nan Li Ph.D. (NCI)

Development Stage
Patent Status
  • U.S. Provisional: U.S. Provisional Patent Application Number 62/795,415, Filed 22 Jan 2019
Therapeutic Area
Tuesday, December 10, 2019