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

Dinutuximab, an immunotherapy targeting GD2, was delivered loacally in a lyophilized silk fibroin foam for the treatment of an orthotopic neuroblastoma mouse model. Silk fibroin foam allows for a sustained release of dinutuximab, causing significant tumor growth inhibition. AbstractImmunotherapy 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 deli ver 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 mai ntenance of bioactivity. The dinut...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research