IgG4 Hinge Containing Nanobody-based CARs Targeting GPC3 for Treating Liver Cancer

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Globally, HCC is the sixth most prevalent cancer and third leading cause of cancer-related morbidity. Standard treatment for HCC is not suitable for a large proportion of liver cancer patients. Part of this is because less than a quarter of HCC patients are surgical candidates for curative-intent treatment. As a result, alternative treatments are needed. Chimeric antigen receptor (CAR) T cell therapy is a promising alternative approach selectively targets targeting tumors via tumor-specific antigens. However, to date, no effective CAR T cell therapy exists for HCC.

Researchers at National Cancer Institute (NCI) developed novel Chimeric Antigen Receptors (CARs) specific for glypican-3 (GPC3) that include short Immunoglobulin subclass 4 (IgG4) and CD28 based hinge domains and the HN3 human single-domain antibody (also called nanobody). The specific HN3 nanobody-IgG4H-CD28TM CAR included in this invention was much more potent both in in vitro cell models and in vivo mouse models.

Researchers at the NCI seek licensing and/or co-development research collaborations for developing new nanobody-based CAR and/or antibody-T-cell receptor therapies for treating liver cancer.