Targeting the immune checkpoint B7-H3 for next-generation cancer immunotherapy

Immune checkpoint inhibitors (ICIs) for programmed death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have become preferred treatment strategies for several advanced cancers. However, response rates for these treatments are limited, which encourages the search for new ICI candidates. Recent reports have underscored significant roles of B7 homolog 3 protein (B7-H3) in tumor immunity and disease progression. While its multifaceted roles are being elucidated, B7-H3 has already entered clinical trials as a therapeutic target. In this review, we overview the recent results of clinical trials evaluating the antitumor activity and safety of B7-H3 targeting drugs. On this basis, we also discuss the challenges and opportunities arising from the application of these drugs. Finally, we point out current gaps to address in the understanding of B7-H3 function and regulation in order to fully unleash the future clinical utility of B7-H3-based therapies for the treatment of cancer.