B7-H3

Class

B7-H3-directed antibody-drug conjugate (topoisomerase I inhibitor payload)

Pathway

immune checkpoint target internalization / DNA-damage payload release

B7-H3, also known as CD276, is a cell-surface protein belonging to the B7 family of immune checkpoint molecules, which normally act as brakes or accelerators on T-cell activity. Cancer cells across many solid tumor types express B7-H3 at high levels while most normal adult tissues express little of it, making the protein an attractive marker for selectively delivering cytotoxic therapy to tumors. Rather than relying solely on blocking its immune-checkpoint signaling, the therapeutic strategy exemplified here uses B7-H3 as a docking site: an antibody or antibody-like molecule binds the protein on the tumor cell surface, is drawn inside the cell through a natural process called internalization, and releases an attached chemotherapy-like payload once inside. In this class, the payload is a topoisomerase I inhibitor, a drug that causes DNA damage in dividing cells, so the target's main job is precise delivery rather than direct biological blockade. This targeted-delivery approach, called an antibody-drug conjugate, matters broadly in oncology because it aims to concentrate cytotoxic activity within tumor tissue while limiting exposure to healthy organs. It is being explored across a range of solid tumors where B7-H3 overexpression has been documented, including tumors with limited existing targeted-therapy options.