Spotlight on dinutuximab in the treatment of high-risk neuroblastoma: development and place in therapy

Michelle E Keyel,1,2 C Patrick Reynolds1–4 1Cancer Center, 2Department of Pediatrics, 3Department of Internal Medicine, 4Department of Cell Biology & Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA Abstract: Neuroblastoma (N...

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Autores principales:	Keyel ME, Reynolds CP
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	neuroblastoma GD2 immunotherapy monoclonal antibody Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/54f44a9d7f4444ea894f7bcee0cad1d9
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spelling	oai:doaj.org-article:54f44a9d7f4444ea894f7bcee0cad1d92021-12-02T04:19:20ZSpotlight on dinutuximab in the treatment of high-risk neuroblastoma: development and place in therapy1177-5491https://doaj.org/article/54f44a9d7f4444ea894f7bcee0cad1d92018-12-01T00:00:00Zhttps://www.dovepress.com/spotlight-on-dinutuximab-in-the-treatment-of-high-risk-neuroblastoma-d-peer-reviewed-article-BTThttps://doaj.org/toc/1177-5491Michelle E Keyel,1,2 C Patrick Reynolds1–4 1Cancer Center, 2Department of Pediatrics, 3Department of Internal Medicine, 4Department of Cell Biology & Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA Abstract: Neuroblastoma (NB) is a pediatric cancer of the sympathetic nervous system which accounts for 8% of childhood cancers. Most NBs express high levels of the disialoganglioside GD2. Several antibodies have been developed to target GD2 on NB, including the human/mouse chimeric antibody ch14.18, known as dinutuximab. Dinutuximab used in combination with granulocyte–macrophage colony-stimulating factor, interleukin-2, and isotretinoin (13-cis-retinoic acid) has a US Food and Drug Administration (FDA)-registered indication for treating high-risk NB patients who achieved at least a partial response to prior first-line multi-agent, multimodality therapy. The FDA registration resulted from a prospective randomized trial assessing the benefit of adding dinutuximab + cytokines to post-myeloablative maintenance therapy for high-risk NB. Dinutuximab has also shown promising antitumor activity when combined with temozolomide and irinotecan in treating NB progressive disease. Clinical activity of dinutuximab and other GD2-targeted therapies relies on the presence of the GD2 antigen on NB cells. Some NBs have been reported as GD2 low or negative, and such tumor cells could be nonresponsive to anti-GD2 therapy. As dinutuximab relies on complement and effector cells to mediate NB killing, factors affecting those components of patient response may also decrease dinutuximab effectiveness. This review summarizes the development of GD2 antibody-targeted therapy, the use of dinutuximab in both up-front and salvage therapy for high-risk NB, and the potential mechanisms of resistance to dinutuximab. Keywords: neuroblastoma, GD2, immunotherapy, monoclonal antibodyKeyel MEReynolds CPDove Medical PressarticleneuroblastomaGD2immunotherapymonoclonal antibodyMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol Volume 13, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	neuroblastoma GD2 immunotherapy monoclonal antibody Medicine (General) R5-920
spellingShingle	neuroblastoma GD2 immunotherapy monoclonal antibody Medicine (General) R5-920 Keyel ME Reynolds CP Spotlight on dinutuximab in the treatment of high-risk neuroblastoma: development and place in therapy
description	Michelle E Keyel,1,2 C Patrick Reynolds1–4 1Cancer Center, 2Department of Pediatrics, 3Department of Internal Medicine, 4Department of Cell Biology & Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA Abstract: Neuroblastoma (NB) is a pediatric cancer of the sympathetic nervous system which accounts for 8% of childhood cancers. Most NBs express high levels of the disialoganglioside GD2. Several antibodies have been developed to target GD2 on NB, including the human/mouse chimeric antibody ch14.18, known as dinutuximab. Dinutuximab used in combination with granulocyte–macrophage colony-stimulating factor, interleukin-2, and isotretinoin (13-cis-retinoic acid) has a US Food and Drug Administration (FDA)-registered indication for treating high-risk NB patients who achieved at least a partial response to prior first-line multi-agent, multimodality therapy. The FDA registration resulted from a prospective randomized trial assessing the benefit of adding dinutuximab + cytokines to post-myeloablative maintenance therapy for high-risk NB. Dinutuximab has also shown promising antitumor activity when combined with temozolomide and irinotecan in treating NB progressive disease. Clinical activity of dinutuximab and other GD2-targeted therapies relies on the presence of the GD2 antigen on NB cells. Some NBs have been reported as GD2 low or negative, and such tumor cells could be nonresponsive to anti-GD2 therapy. As dinutuximab relies on complement and effector cells to mediate NB killing, factors affecting those components of patient response may also decrease dinutuximab effectiveness. This review summarizes the development of GD2 antibody-targeted therapy, the use of dinutuximab in both up-front and salvage therapy for high-risk NB, and the potential mechanisms of resistance to dinutuximab. Keywords: neuroblastoma, GD2, immunotherapy, monoclonal antibody
format	article
author	Keyel ME Reynolds CP
author_facet	Keyel ME Reynolds CP
author_sort	Keyel ME
title	Spotlight on dinutuximab in the treatment of high-risk neuroblastoma: development and place in therapy
title_short	Spotlight on dinutuximab in the treatment of high-risk neuroblastoma: development and place in therapy
title_full	Spotlight on dinutuximab in the treatment of high-risk neuroblastoma: development and place in therapy
title_fullStr	Spotlight on dinutuximab in the treatment of high-risk neuroblastoma: development and place in therapy
title_full_unstemmed	Spotlight on dinutuximab in the treatment of high-risk neuroblastoma: development and place in therapy
title_sort	spotlight on dinutuximab in the treatment of high-risk neuroblastoma: development and place in therapy
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/54f44a9d7f4444ea894f7bcee0cad1d9
work_keys_str_mv	AT keyelme spotlightondinutuximabinthetreatmentofhighriskneuroblastomadevelopmentandplaceintherapy AT reynoldscp spotlightondinutuximabinthetreatmentofhighriskneuroblastomadevelopmentandplaceintherapy
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Spotlight on dinutuximab in the treatment of high-risk neuroblastoma: development and place in therapy

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