B7H3 (B7 homolog 3), also known as CD276. is a member of the B7 family of immune checkpoint proteins. Initially identified in 2001. it is a transmembrane glycoprotein with extracellular immunoglobulin-like domains. While its exact physiological role remains debated, B7H3 appears to play dual roles in immune regulation. It can suppress T-cell activation and cytokine production, contributing to immune evasion in tumors, but also shows context-dependent co-stimulatory effects in certain settings.
B7H3 is minimally expressed in normal tissues but overexpressed across multiple cancers, including lung, prostate, breast, and glioblastoma. Its elevated expression correlates with poor prognosis, tumor progression, metastasis, and therapy resistance. This tumor-selective expression pattern, combined with limited normal tissue exposure, makes B7H3 an attractive therapeutic target.
Current research focuses on developing B7H3-directed therapies, including monoclonal antibodies, antibody-drug conjugates (ADCs), bispecific antibodies, and CAR-T cells. Clinical-stage agents like enoblituzumab (Fc-optimized mAb) and ¹³¹I-omburtamab (radioimmunotherapy) have shown preliminary safety and efficacy. Challenges include incomplete understanding of its binding partners, signaling mechanisms, and potential on-target/off-tumor toxicity. Ongoing studies aim to clarify B7H3's biology while advancing targeted immunotherapies.