Immunological mechanisms and antibody-drug conjugates targeting B7-H3 and B7-H4 in ovarian cancer

Abstract

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.