Local delivery of dinutuximab from lyophilized silk fibroin foams for treatment of an orthotopic neuroblastoma model

Abstract

Abstract Immunotherapy targeting GD2 is a primary treatment for patients with high‐risk neuroblastoma. Dinutuximab is a monoclonal antibody with great clinical promise but is limited by side effects such as severe pain. Local delivery has emerged as a potential mechanism to deliver higher doses of therapeutics into the tumor bed, while limiting systemic toxicity. We aim to deliver dinutuximab locally in a lyophilized silk fibroin foam for the treatment of an orthotopic neuroblastoma mouse model. Dinutuximab‐loaded silk fibroin foams were fabricated through lyophilization. In vitro release profile and bioactivity of the release through complement‐dependent cytotoxicity were characterized. MYCN‐amplified neuroblastoma cells (KELLY) were injected into the left gland of mice to generate an orthotopic neuroblastoma model. Once the tumor volume reached 100 mm3, dinutuximab‐, human IgG‐, or buffer‐loaded foams were implanted into the tumor and growth was monitored using high‐resolution ultrasound. Post‐resection histology was performed on tumors. Dinutuximab‐loaded silk fibroin foams exhibited a burst release, with slow release thereafter in vitro with maintenance of bioactivity. The dinutuximab‐loaded foam significantly inhibited xenograft tumor growth compared to IgG‐ and buffer‐loaded foams. Histological analysis revealed the presence of dinutuximab within the tumor and neutrophils and macrophages infiltrating into dinutuximab‐loaded silk foam. Tumors treated with local dinutuximab had decreased MYCN expression on histology compared to control or IgG‐treated tumors. Silk fibroin foams offer a mechanism for local release of dinutuximab within the neuroblastoma tumor. This local delivery achieved a significant decrease in tumor growth rate in a mouse orthotopic tumor model.

Keywords

• Ch14.18
• dinutuximab
• immunotherapy
• local delivery
• neuroblastoma
• silk fibroin