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Disialoganglioside GD2-Targeted Near-Infrared Photoimmunotherapy (NIR-PIT) in Tumors of Neuroectodermal Origin

Disialoganglioside (GD2) is a subtype of glycolipids that is highly expressed in tumors of neuroectodermal origins, such as neuroblastoma and osteosarcoma. Its limited expression in normal tissues makes GD2 a potential target for precision therapy. Several anti-GD2 monoclonal antibodies are currentl...

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Autores principales: Inagaki, Fuyuki F., Kato, Takuya, Furusawa, Aki, Okada, Ryuhei, Wakiyama, Hiroaki, Furumoto, Hideyuki, Okuyama, Shuhei, Choyke, Peter L., Kobayashi, Hisataka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612122/
https://www.ncbi.nlm.nih.gov/pubmed/36297471
http://dx.doi.org/10.3390/pharmaceutics14102037
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author Inagaki, Fuyuki F.
Kato, Takuya
Furusawa, Aki
Okada, Ryuhei
Wakiyama, Hiroaki
Furumoto, Hideyuki
Okuyama, Shuhei
Choyke, Peter L.
Kobayashi, Hisataka
author_facet Inagaki, Fuyuki F.
Kato, Takuya
Furusawa, Aki
Okada, Ryuhei
Wakiyama, Hiroaki
Furumoto, Hideyuki
Okuyama, Shuhei
Choyke, Peter L.
Kobayashi, Hisataka
author_sort Inagaki, Fuyuki F.
collection PubMed
description Disialoganglioside (GD2) is a subtype of glycolipids that is highly expressed in tumors of neuroectodermal origins, such as neuroblastoma and osteosarcoma. Its limited expression in normal tissues makes GD2 a potential target for precision therapy. Several anti-GD2 monoclonal antibodies are currently in clinical use and have had moderate success. Near-infrared photoimmunotherapy (NIR-PIT) is a cancer therapy that arms antibodies with IRDye700DX (IR700) and then exposes this antibody–dye conjugate (ADC) to NIR light at a wavelength of 690 nm. NIR light irradiation induces a profound photochemical response in IR700, resulting in protein aggregates that lead to cell membrane damage and death. In this study, we examined the feasibility of GD2-targeted NIR-PIT. Although GD2, like other glycolipids, is only located in the outer leaflet of the cell membrane, the aggregates formation exerted sufficient physical force to disrupt the cell membrane and kill target cells in vitro. In in vivo studies, tumor growth was significantly inhibited after GD2-targeted NIR-PIT, resulting in prolonged survival. Following GD2-targeted NIR-PIT, activation of host immunity was observed. In conclusion, GD2-targeted NIR-PIT was similarly effective to the conventional protein-targeted NIR-PIT. This study demonstrates that membrane glycolipid can be a new target of NIR-PIT.
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spelling pubmed-96121222022-10-28 Disialoganglioside GD2-Targeted Near-Infrared Photoimmunotherapy (NIR-PIT) in Tumors of Neuroectodermal Origin Inagaki, Fuyuki F. Kato, Takuya Furusawa, Aki Okada, Ryuhei Wakiyama, Hiroaki Furumoto, Hideyuki Okuyama, Shuhei Choyke, Peter L. Kobayashi, Hisataka Pharmaceutics Article Disialoganglioside (GD2) is a subtype of glycolipids that is highly expressed in tumors of neuroectodermal origins, such as neuroblastoma and osteosarcoma. Its limited expression in normal tissues makes GD2 a potential target for precision therapy. Several anti-GD2 monoclonal antibodies are currently in clinical use and have had moderate success. Near-infrared photoimmunotherapy (NIR-PIT) is a cancer therapy that arms antibodies with IRDye700DX (IR700) and then exposes this antibody–dye conjugate (ADC) to NIR light at a wavelength of 690 nm. NIR light irradiation induces a profound photochemical response in IR700, resulting in protein aggregates that lead to cell membrane damage and death. In this study, we examined the feasibility of GD2-targeted NIR-PIT. Although GD2, like other glycolipids, is only located in the outer leaflet of the cell membrane, the aggregates formation exerted sufficient physical force to disrupt the cell membrane and kill target cells in vitro. In in vivo studies, tumor growth was significantly inhibited after GD2-targeted NIR-PIT, resulting in prolonged survival. Following GD2-targeted NIR-PIT, activation of host immunity was observed. In conclusion, GD2-targeted NIR-PIT was similarly effective to the conventional protein-targeted NIR-PIT. This study demonstrates that membrane glycolipid can be a new target of NIR-PIT. MDPI 2022-09-24 /pmc/articles/PMC9612122/ /pubmed/36297471 http://dx.doi.org/10.3390/pharmaceutics14102037 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Inagaki, Fuyuki F.
Kato, Takuya
Furusawa, Aki
Okada, Ryuhei
Wakiyama, Hiroaki
Furumoto, Hideyuki
Okuyama, Shuhei
Choyke, Peter L.
Kobayashi, Hisataka
Disialoganglioside GD2-Targeted Near-Infrared Photoimmunotherapy (NIR-PIT) in Tumors of Neuroectodermal Origin
title Disialoganglioside GD2-Targeted Near-Infrared Photoimmunotherapy (NIR-PIT) in Tumors of Neuroectodermal Origin
title_full Disialoganglioside GD2-Targeted Near-Infrared Photoimmunotherapy (NIR-PIT) in Tumors of Neuroectodermal Origin
title_fullStr Disialoganglioside GD2-Targeted Near-Infrared Photoimmunotherapy (NIR-PIT) in Tumors of Neuroectodermal Origin
title_full_unstemmed Disialoganglioside GD2-Targeted Near-Infrared Photoimmunotherapy (NIR-PIT) in Tumors of Neuroectodermal Origin
title_short Disialoganglioside GD2-Targeted Near-Infrared Photoimmunotherapy (NIR-PIT) in Tumors of Neuroectodermal Origin
title_sort disialoganglioside gd2-targeted near-infrared photoimmunotherapy (nir-pit) in tumors of neuroectodermal origin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612122/
https://www.ncbi.nlm.nih.gov/pubmed/36297471
http://dx.doi.org/10.3390/pharmaceutics14102037
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