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Local delivery of dinutuximab from lyophilized silk fibroin foams for treatment of an orthotopic neuroblastoma model
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 therapeuti...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163090/ https://www.ncbi.nlm.nih.gov/pubmed/32096344 http://dx.doi.org/10.1002/cam4.2936 |
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author | Ornell, Kimberly J. Taylor, Jordan S. Zeki, Jasmine Ikegaki, Naohiko Shimada, Hiroyuki Coburn, Jeannine M. Chiu, Bill |
author_facet | Ornell, Kimberly J. Taylor, Jordan S. Zeki, Jasmine Ikegaki, Naohiko Shimada, Hiroyuki Coburn, Jeannine M. Chiu, Bill |
author_sort | Ornell, Kimberly J. |
collection | PubMed |
description | 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 mm(3), 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. |
format | Online Article Text |
id | pubmed-7163090 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71630902020-04-20 Local delivery of dinutuximab from lyophilized silk fibroin foams for treatment of an orthotopic neuroblastoma model Ornell, Kimberly J. Taylor, Jordan S. Zeki, Jasmine Ikegaki, Naohiko Shimada, Hiroyuki Coburn, Jeannine M. Chiu, Bill Cancer Med Cancer Biology 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 mm(3), 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. John Wiley and Sons Inc. 2020-02-24 /pmc/articles/PMC7163090/ /pubmed/32096344 http://dx.doi.org/10.1002/cam4.2936 Text en © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Cancer Biology Ornell, Kimberly J. Taylor, Jordan S. Zeki, Jasmine Ikegaki, Naohiko Shimada, Hiroyuki Coburn, Jeannine M. Chiu, Bill Local delivery of dinutuximab from lyophilized silk fibroin foams for treatment of an orthotopic neuroblastoma model |
title | Local delivery of dinutuximab from lyophilized silk fibroin foams for treatment of an orthotopic neuroblastoma model |
title_full | Local delivery of dinutuximab from lyophilized silk fibroin foams for treatment of an orthotopic neuroblastoma model |
title_fullStr | Local delivery of dinutuximab from lyophilized silk fibroin foams for treatment of an orthotopic neuroblastoma model |
title_full_unstemmed | Local delivery of dinutuximab from lyophilized silk fibroin foams for treatment of an orthotopic neuroblastoma model |
title_short | Local delivery of dinutuximab from lyophilized silk fibroin foams for treatment of an orthotopic neuroblastoma model |
title_sort | local delivery of dinutuximab from lyophilized silk fibroin foams for treatment of an orthotopic neuroblastoma model |
topic | Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163090/ https://www.ncbi.nlm.nih.gov/pubmed/32096344 http://dx.doi.org/10.1002/cam4.2936 |
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