REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicImmunological Aspects and Immunotherapy in Gynecologic CancersView all 23 articles
Immunological Mechanisms and Antibody-Drug Conjugates targeting B7-H3 and B7-H4 in Ovarian Cancer
Provisionally accepted
- 1Saint George Hospital Saint George Cancer Care Centre, Kogarah, Australia
- 2Wollongong Hospital, Wollongong, Australia
- 3Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland
- 4Hospital Universitario 12 de Octubre, Madrid, Spain
- 5The University of Sydney, Darlington, Australia
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Ovarian cancer remains the most lethal gynecologic malignancy, with immune evasion a major driver of therapeutic resistance and disease progression. Among novel targets, the immune checkpoint molecules B7-H3 and B7-H4 have been recognized for their potent immunosuppressive roles and selective overexpression in ovarian tumors. This review examines the immunological mechanisms shaping B7-H3 and B7-H4 activity within the ovarian tumor microenvironment, their role in facilitating immune escape, and their association with poor clinical outcomes. The development of antibody–drug conjugates targeting B7-H3 and B7-H4 offers a novel approach to deliver potent cytotoxic therapy with tumor specificity. Preclinical models and early-phase clinical studies demonstrate encouraging antitumor activity, including in treatment-resistant disease. By integrating advances in tumor immunobiology and ADC technology, this review explores how targeting B7-H3 and B7-H4 could reshape therapeutic strategies in ovarian cancer.
Keywords: ovarian cancer, anti-body drug conjugates, B7-H3, B7-H4, Tumormicroenvironment, Immunotherapy, Drug Resistance
Received: 11 Aug 2025; Accepted: 31 Oct 2025.
Copyright: © 2025 Brown, Colombo, Madariaga and Kasherman. 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) or licensor 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: Lawrence Kasherman, lawrence.kasherman@health.nsw.gov.au
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