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Targeting B7-H3-A Novel Strategy for the Design of Anticancer Agents for Extracranial Pediatric Solid Tumors
Petar Rasic1, Marija Jeremic2, Rada Jeremic3
1Department of Abdominal Surgery, Mother and Child Health Care Institute of Serbia "Dr. Vukan Cupic", 11000 Belgrade, Serbia.
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 cell-cycle 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 studies, including in vitro, in vivo, and clinical research, and explains all the benefits and potential obstacles of targeting B7-H3 by novel immunotherapeutic agents designed to treat malignant extracranial solid tumors of childhood.
Insights
The B7-H3 checkpoint molecule shows promise for treating pediatric solid tumors (PSTs). Targeting B7-H3 with immunotherapies like antibody-drug conjugates and CAR-T cells demonstrates significant anti-tumor effects in preclinical and clinical studies.
Area of Science:
- Immunology
- Oncology
- Pediatric Medicine
Background:
- B7-H3 is a checkpoint molecule highly expressed in pediatric solid tumors (PSTs) but not in normal tissues.
- B7-H3 influences tumor behavior through immune evasion, invasion, and cell-cycle disruption.
- Targeting B7-H3 offers a promising strategy for PST immunotherapy.
Purpose of the Study:
- To review current data on B7-H3 as a therapeutic target for PSTs.
- To summarize the benefits and potential obstacles of B7-H3-targeted immunotherapies.
- To discuss novel immunotherapeutic agents for childhood malignant extracranial solid tumors.
Main Methods:
- In vitro studies assessing B7-H3 knockdown effects on tumor cells.
- In vivo studies using preclinical models with B7-H3-targeted therapies (ADCs, CAR-T cells).
- Clinical studies evaluating B7-H3-targeting antibody-radioimmunoconjugates.
Main Results:
- B7-H3 knockdown reduced tumor proliferation, migration, and growth, enhancing anti-tumor immunity.
- Antibody-drug conjugates and CAR-T cells showed significant anti-tumor effects in preclinical PST models.
- Clinical trials confirmed potent anti-tumor activity of B7-H3-targeting agents in metastatic neuroblastoma.
Conclusions:
- B7-H3 is a validated target for immunotherapy in pediatric solid tumors.
- Various B7-H3-targeted immunotherapeutic strategies show significant potential.
- Further research and clinical development are warranted to overcome obstacles and optimize treatment for childhood cancers.
