Monoclonal antibodies targeting glypican-2 (GPC2) and use thereof

US11066479B2 · kind B2 · utility

Assignee

• The United States of America, as represented by the Secretary, Department of Health and Human Services · US

Inventors

• Mitchell Ho · Urbana, US
• Nan Li · Tianjin, CN
• Dimiter S. Dimitrov · Frederick, US

Key dates

• Filing date: Jul 20, 2017
• Grant date: Jul 20, 2021
• Expiry date: Jul 5, 2038

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2310/20
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A panel of human variable heavy (VH) single domain monoclonal antibodies specific for cell-surface glypican-2 (GPC2) are described. Methods for the diagnosis and treatment and GPC2-positive cancer are also described. Recombinant immunotoxins comprised of a GPC2-specific VH domain antibody and a clinically used form of Pseudomonas exotoxin A (PE38) were generated and shown to inhibit GPC2-positive neuroblastoma tumor cell growth and inhibit neuroblastoma xenograft growth in nude mice, without significant toxicity. Chimeric antigen receptors comprising a GPC2-specific VH single domain antibody are also described. T cells expressing the GPC2-specific CARs potently killed GPC2-positive neuroblastoma cells in a dose-dependent manner.