Low-affinity binding of anti-B7-H3 clone MJ18 to murine B7-H3 fails to induce tumor regression.

The immune checkpoint molecule B7-H3 is regarded as one of the most promising therapeutic targets for the treatment of human cancers. B7-H3 is highly expressed in many cancers, and its expression has been associated to impaired antitumor immunity and poor patient prognosis. In immunocompetent mouse tumor models, genetic deletion of B7-H3 in tumor cells enhances antitumor immune response leading to tumor shrinkage. The underlying mechanisms of B7-H3 inhibitory function remain largely uncharacterized and the identity of potential cognate(s) receptor(s) of B7-H3 is still to be defined. To better understand B7-H3 function in vivo, several studies have employed MJ18, a monoclonal antibody reported to bind murine B7-H3 and blocks its immune-inhibitory function. In this brief research report, we show that MJ18 binds B7-H3 with very low affinity and does not induce tumor regression in three mouse models responsive to B7-H3 genetic deletion. Given the high profile of B7-H3 as a therapeutic target for human cancers, our work emphasizes that murine B7-H3 studies using the MJ18 antibody should be interpreted with caution. Finally, we hope that our study will motivate the scientific community to establish much-needed validated research tools to study B7-H3 biology in mouse models.