Targeting B7-H3—A Novel Strategy for the Design of Anticancer Agents for Extracranial Pediatric Solid Tumors Treatment - Review

Sep 24, 2026

Uploaded by Oliver

Recent scientific data recognize the B7-H3 checkpoint molecule as a promising target for immunotherapy of pediatric solid tumors (PSTs). B7-H3 is highly expressed in extracranial PSTs, including neuroblastoma, rhabdomyosarcoma, nephroblastoma, osteosarcoma, and Ewing sarcoma, while remaining absent or very low in normal tissues and organs. B7-H3 influences childhood malignant solid neoplasms through immune evasion, tumor invasion, and disruption of cell-cycle regulation. Studies report that B7-H3 knockdown reduces proliferation and migration, suppresses tumor growth, and strengthens anti-tumor immune responses. Antibody-drug conjugates and B7-H3-targeting CAR-T cells show potent preclinical activity, and clinical evidence supports strong anti-tumor effects in metastatic neuroblastoma, with benefits and obstacles discussed across in vitro, in vivo, and clinical research.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Abstract

Keywords

Introduction

Pediatric solid tumors and key examples

Limits of current therapies

Rationale for B7-H3-targeted immunotherapy

molecules Review Targeting B7-H3—A Novel Strategy for the Design of Anticancer Agents for Extracranial Pediatric Solid Tumors Treatment Petar Rasic 1, *, Marija Jeremic 2, Rada Jeremic 3, Marija Dusanovic Pjevic 4, Milica Rasic 4, Slavisa M. Djuricic 5,6, Maja Milickovic 1,7, Miroslav Vukadin 1, Tanja Mijovic 1 and Djordje Savic 1,7 Citation: Rasic, P.; Jeremic, M.; Jeremic, R.; Dusanovic Pjevic, M.; Rasic, M.; Djuricic, S.M.; Milickovic, M.; Vukadin, M.; Mijovic, T.; Savic, D. Targeting B7-H3—A Novel Strategy for the Design of Anticancer Agents for Extracranial Pediatric Solid Tumors Treatment. Molecules 2023, 28, 3356. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)molecules28083356 Academic Editor: Małgorzata Jele ´n Received: 14 March 2023 Revised: 5 April 2023 Accepted: 7 April 2023 Published: 11 April 2023 Copyright: © 2023 by the authors. 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://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Abdominal Surgery, Mother and Child Health Care Institute of Serbia “Dr. Vukan Cupic”, 11000 Belgrade, Serbia; [majacvetkovicmilickovic@gmail.com](majacvetkovicmilickovic@gmail.com) (M.M.); [miroslav_vukadin@yahoo.com](miroslav_vukadin@yahoo.com) (M.V.); [tanja.sav@gmail.com](tanja.sav@gmail.com) (T.M.); [djordje.savic@imd.org.rs](djordje.savic@imd.org.rs) (D.S.) 2 Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; [marija.jeremic@med.bg.ac.rs](marija.jeremic@med.bg.ac.rs) 3 Institute of Medical Physiology “Richard Burian”, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; [rada.jeremic@med.bg.ac.rs](rada.jeremic@med.bg.ac.rs) 4 Institute of Human Genetics, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; [marija.dusanovic-pjevic@med.bg.ac.rs](marija.dusanovic-pjevic@med.bg.ac.rs) (M.D.P.); [milica.rasic@med.bg.ac.rs](milica.rasic@med.bg.ac.rs) (M.R.) 5 Department of Clinical Pathology, Mother and Child Health Care Institute of Serbia “Dr. Vukan Cupic”, 11000 Belgrade, Serbia; [slavisa.djuricic@med.unibl.org](slavisa.djuricic@med.unibl.org) 6 Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina 7 Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia * [Correspondence: perasrv@yahoo.com](Correspondence: perasrv@yahoo.com) Abstract: Recent scientiﬁc data recognize the B7-H3 checkpoint molecule as a potential target for immunotherapy of pediatric solid tumors (PSTs) . B7-H3 is highly expressed in extracranial PSTs such as neuroblastoma, rhabdomyosarcoma, nephroblastoma, osteosarcoma, and Ewing sarcoma, whereas its expression is absent or very low in normal tissues and organs. The inﬂuence of B7-H3 on the biological behavior of malignant solid neoplasms of childhood is expressed through different molecular mechanisms, including stimulation of immune evasion and tumor invasion, and cellcycle disruption. It has been shown that B7-H3 knockdown decreased tumor cell proliferation and migration, suppressed tumor growth, and enhanced anti-tumor immune response in some pediatric solid cancers. Antibody-drug conjugates targeting B7-H3 exhibited profound anti-tumor effects against preclinical models of pediatric solid malignancies. Moreover, B7-H3-targeting chimeric antigen receptor (CAR)-T cells demonstrated signiﬁcant in vivo activity against different xenograft models of neuroblastoma, Ewing sarcoma, and osteosarcoma. Finally, clinical studies demonstrated the potent anti-tumor activity of B7-H3-targeting antibody-radioimmunoconjugates in metastatic neuroblastoma. This review summarizes the established data from various PST-related st

FAQs

What is B7-H3 and why is it considered a target for pediatric solid tumors?

B7-H3 is a checkpoint molecule that is highly expressed in extracranial pediatric solid tumors but absent or very low in normal tissues. The review highlights its potential as an immunotherapy target based on its biological role in malignancies.

How does B7-H3 affect the behavior of childhood malignant solid tumors?

The review describes multiple mechanisms, including stimulation of immune evasion and tumor invasion, as well as disruption of cell-cycle regulation.

What therapeutic strategies targeting B7-H3 are discussed, and what evidence supports them?

The review covers B7-H3 knockdown effects, antibody-drug conjugates, and B7-H3-targeting CAR-T cells, with reported anti-tumor activity in preclinical models. It also references clinical studies showing potent anti-tumor effects in metastatic neuroblastoma.

Sep 24, 2026

Uploaded by Oliver