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Immunotherapeutic Targeting of GPC3 in Pediatric Solid Embryonal Tumors
Glypican 3 (GPC3) is a heparan sulfate proteoglycan and cell surface oncofetal protein which is highly expressed on a variety of pediatric solid embryonal tumors including the majority of hepatoblastomas, Wilms tumors, rhabdoid tumors, certain germ cell tumor subtypes, and a minority of rhabdomyosar...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401603/ https://www.ncbi.nlm.nih.gov/pubmed/30873384 http://dx.doi.org/10.3389/fonc.2019.00108 |
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author | Ortiz, Michael V. Roberts, Stephen S. Glade Bender, Julia Shukla, Neerav Wexler, Leonard H. |
author_facet | Ortiz, Michael V. Roberts, Stephen S. Glade Bender, Julia Shukla, Neerav Wexler, Leonard H. |
author_sort | Ortiz, Michael V. |
collection | PubMed |
description | Glypican 3 (GPC3) is a heparan sulfate proteoglycan and cell surface oncofetal protein which is highly expressed on a variety of pediatric solid embryonal tumors including the majority of hepatoblastomas, Wilms tumors, rhabdoid tumors, certain germ cell tumor subtypes, and a minority of rhabdomyosarcomas. Via both its core protein and heparan sulfate side chains, GPC3 activates the canonical Wnt/β-catenin pathway, which is frequently overexpressed in these malignancies. Loss of function mutations in GPC3 lead to Simpson-Golabi-Behmel Syndrome, an X-linked overgrowth condition with a predisposition to GPC3-expressing cancers including hepatoblastoma and Wilms tumor. There are several immunotherapeutic approaches to targeting GPC3, including vaccines, monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, cytolytic T lymphocytes, and CAR T cells. These therapies offer a potentially novel means to target these pediatric solid embryonal tumors. A key pediatric-specific consideration of GPC3-targeted immunotherapeutics is that GPC3 can be physiologically expressed in normal tissues during the first year of life, particularly in the liver and kidney. In summary, this article reviews the current evidence for targeting childhood cancers with GPC3-directed immunotherapies. |
format | Online Article Text |
id | pubmed-6401603 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64016032019-03-14 Immunotherapeutic Targeting of GPC3 in Pediatric Solid Embryonal Tumors Ortiz, Michael V. Roberts, Stephen S. Glade Bender, Julia Shukla, Neerav Wexler, Leonard H. Front Oncol Oncology Glypican 3 (GPC3) is a heparan sulfate proteoglycan and cell surface oncofetal protein which is highly expressed on a variety of pediatric solid embryonal tumors including the majority of hepatoblastomas, Wilms tumors, rhabdoid tumors, certain germ cell tumor subtypes, and a minority of rhabdomyosarcomas. Via both its core protein and heparan sulfate side chains, GPC3 activates the canonical Wnt/β-catenin pathway, which is frequently overexpressed in these malignancies. Loss of function mutations in GPC3 lead to Simpson-Golabi-Behmel Syndrome, an X-linked overgrowth condition with a predisposition to GPC3-expressing cancers including hepatoblastoma and Wilms tumor. There are several immunotherapeutic approaches to targeting GPC3, including vaccines, monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, cytolytic T lymphocytes, and CAR T cells. These therapies offer a potentially novel means to target these pediatric solid embryonal tumors. A key pediatric-specific consideration of GPC3-targeted immunotherapeutics is that GPC3 can be physiologically expressed in normal tissues during the first year of life, particularly in the liver and kidney. In summary, this article reviews the current evidence for targeting childhood cancers with GPC3-directed immunotherapies. Frontiers Media S.A. 2019-02-26 /pmc/articles/PMC6401603/ /pubmed/30873384 http://dx.doi.org/10.3389/fonc.2019.00108 Text en Copyright © 2019 Ortiz, Roberts, Glade Bender, Shukla and Wexler. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Ortiz, Michael V. Roberts, Stephen S. Glade Bender, Julia Shukla, Neerav Wexler, Leonard H. Immunotherapeutic Targeting of GPC3 in Pediatric Solid Embryonal Tumors |
title | Immunotherapeutic Targeting of GPC3 in Pediatric Solid Embryonal Tumors |
title_full | Immunotherapeutic Targeting of GPC3 in Pediatric Solid Embryonal Tumors |
title_fullStr | Immunotherapeutic Targeting of GPC3 in Pediatric Solid Embryonal Tumors |
title_full_unstemmed | Immunotherapeutic Targeting of GPC3 in Pediatric Solid Embryonal Tumors |
title_short | Immunotherapeutic Targeting of GPC3 in Pediatric Solid Embryonal Tumors |
title_sort | immunotherapeutic targeting of gpc3 in pediatric solid embryonal tumors |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401603/ https://www.ncbi.nlm.nih.gov/pubmed/30873384 http://dx.doi.org/10.3389/fonc.2019.00108 |
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