Immunotherapeutic targeting of GPC3 in pediatric solid embryonal tumors Review

   


Authors: Ortiz, M. V.; Roberts, S. S.; Glade Bender, J.; Shukla, N.; Wexler, L. H.
Review Title: Immunotherapeutic targeting of GPC3 in pediatric solid embryonal tumors
Abstract: Glypican 3 (GPC 3 ) 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, GPC 3 activates the canonical Wnt/β-catenin pathway, which is frequently overexpressed in these malignancies. Loss of function mutations in GPC 3 lead to Simpson-Golabi-Behmel Syndrome, an X-linked overgrowth condition with a predisposition to GPC 3 -expressing cancers including hepatoblastoma and Wilms tumor. There are several immunotherapeutic approaches to targeting GPC 3 , 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 GPC 3 -targeted immunotherapeutics is that GPC 3 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 GPC 3 -directed immunotherapies. Copyright © 2019 Ortiz, Roberts, Glade Bender, Shukla and Wexler.
Keywords: immunotherapy; neuroblastoma; rhabdomyosarcoma; rhabdoid tumor; glypican 3; hepatoblastoma (hb); germ cell tumors (gct); wilms tumor (wt)
Journal Title: Frontiers in Oncology
Volume: 9
ISSN: 2234-943X
Publisher: Frontiers Media S.A.  
Date Published: 2019-02-26
Start Page: 108
Language: English
DOI: 10.3389/fonc.2019.00108
PROVIDER: scopus
PMCID: PMC6401603
PUBMED: 30873384
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85063269610&doi=10.3389%2ffonc.2019.00108&partnerID=40&md5=d6ff23e09aa9dec61f8ca4de67800f45
Notes: Review -- Export Date: 1 May 2019 -- Source: Scopus
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MSK Authors
  1. Leonard H Wexler
    191 Wexler
  2. Neerav Shukla
    159 Shukla
  3. Stephen Stacy Roberts
    107 Roberts
  4. Michael Vincent Ortiz
    61 Ortiz
  5. Julia L Glade Bender
    85 Glade Bender
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