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

Autor: Jordan S. Taylor, Hiroyuki Shimada, Jeannine M. Coburn, Jasmine Zeki, Naohiko Ikegaki, Kimberly J. Ornell, Bill Chiu
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Cancer Research
medicine.drug_class
medicine.medical_treatment
Fibroin
Mice
Nude
Antineoplastic Agents
Apoptosis
Monoclonal antibody
lcsh:RC254-282
03 medical and health sciences
Mice
neuroblastoma
0302 clinical medicine
Drug Delivery Systems
Ch14.18
Neuroblastoma
medicine
Tumor Cells
Cultured
Animals
Humans
Radiology
Nuclear Medicine and imaging
Cytotoxicity
Original Research
Cancer Biology
Cell Proliferation
Chemistry
dinutuximab
fungi
Dinutuximab
Antibodies
Monoclonal
Histology
Immunotherapy
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Xenograft Model Antitumor Assays
In vitro
Disease Models
Animal
030104 developmental biology
Freeze Drying
Oncology
silk fibroin
030220 oncology & carcinogenesis
Cancer research
Female
immunotherapy
Fibroins
local delivery
Zdroj: Cancer Medicine, Vol 9, Iss 8, Pp 2891-2903 (2020)
Cancer Medicine
ISSN: 2045-7634
Popis: 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.
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.
Databáze: OpenAIRE
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