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Front. Oncol. | doi: 10.3389/fonc.2019.00108

Immunotherapeutic Targeting of GPC3 in Pediatric Solid Embryonal Tumors

  • 1Department of Pediatrics, Memorial Sloan Kettering Cancer Center, United States

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 its heparan sulfate side chains, GPC3 activates the canonical Wnt/β-catenin and insulin-like growth factor signaling pathways, which are 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.

Keywords: Glypican 3, Hepatoblastoma (HB), germ cell tumor (GCT), Wilms tumor (WT), Rhabdoid Tumor, Rhabdomyosarcoma, Neuroblastoma, Immunotherapy

Received: 04 Dec 2018; Accepted: 05 Feb 2019.

Edited by:

Giuliana Cassinelli, National Tumor Institute (Italy), Italy

Reviewed by:

Min H. Kang, Texas Tech University Health Sciences Center, United States
Jorge Filmus, Sunnybrook Research Institute (SRI), Canada  

Copyright: © 2019 Ortiz, Roberts, Glade Bender, Shukla and Wexler. 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.

* Correspondence:
Dr. Michael V. Ortiz, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States,
Dr. Leonard H. Wexler, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States, wexlerl@MSKCC.ORG