Human Monoclonal Antibodies Targeting Glypican-2 in Neuroblastoma
Neuroblastoma is a rare pediatric cancer that affects one in every hundred thousand children under the age of fifteen in the United States. Current standards of care are chemotherapy and surgery, followed by stem-cell treatments, radiation and anti-ganglioside antibody therapy, which yield an average three-year survival rate of 10-45%. This demonstrates a need for more effective therapies.
Glypican-2 (GPC2) is a cell surface protein that has been shown to be preferentially expressed on numerous pediatric cancers, including neuroblastoma. Due to this preferential expression, GPC2 represents a potential candidate for targeted therapy.
Researchers at the National Cancer Institute’s Laboratory of Molecular Biology (NCI LMB) have developed and isolated several single domain monoclonal human antibodies against GPC2. This technology covers the naked GPC2 antibodies as well as their use as targeting domains in recombinant immunotoxins (RITs) and chimeric antigen receptors (CARs). RITs (using clones LH1, LH4, or LH7) and CARs (using LH7) have shown specific killing activity against GPC2-expressing cells, suggesting that these candidates may be further developed as therapeutics.
The technology has been validated with in-vitro studies (human anti-GPC2 RITs and CARs can bind to, and kill, GPC2-positive tumor cells) and the researchers are currently developing mouse models to further develop GPC2-targeted therapies.
Competitive Advantages:
- First to market potential – No current clinical trials with GPC2-targeted therapies
- Human antibody with high specificity and binding to targets results in less non-specific cell killing, therefore fewer potential side-effects for the patient
- Small size of single domain antibodies enhances stability, solubility, and target recognition
Commercial Applications:
- Therapeutic applications include unconjugated antibodies and use as targeting moieties for immunoconjugates such as CARs, ADCs, immunotoxins, and bispecific antibodies
- Diagnostic agent for detecting and monitoring target-expressing malignancies