B7-H3

B7-H3

Summary

B7-H3 (CD276) is a tumor-associated immune-related protein that is markedly upregulated across EGFR-positive malignancies while showing minimal expression in healthy tissues, making it a tumor-selective binding target. It can mediate cis-inhibition in the context of an EGFR/B7-H3 bispecific antibody, supporting a mechanism for enhanced anti-tumor efficacy with reduced toxicity. B7-H3 is also elevated in the immune-resistant colorectal cancer organoid fraction, linking it to colorectal cancer immune escape and resistance phenotypes. In addition, B7-H3-enriched exosomes influence exosome biogenesis, signaling, and tumor progression, and are implicated in modulation of the tumor microenvironment to promote immune evasion, metastasis, and therapy resistance. Therapeutically, it is being targeted by next-generation antibody-drug conjugates and bispecific T cell engagers, including approaches relevant to pediatric solid tumors. Reported pathway associations include activation of PI3K and STAT3 signaling, consistent with broader pro-tumor functions.

Key Findings

EGFR-positive malignancies and bispecific targeting

  • A 2026 Nature Communications study (PMID:41735305) showed that ibi334 uses B7-H3 for tumor-selective binding and mediates cis-inhibition of EGFR, enhancing anti-tumor efficacy while minimizing toxicities. (PMID:41735305)
  • B7-H3 was described as markedly upregulated across EGFR-positive malignancies with minimal expression in healthy tissues, supporting its use as a selective therapeutic target. (PMID:41735305)
  • The reported mechanism links B7-H3 to cis-inhibition within a bispecific antibody format, highlighting a functional role beyond simple surface antigen expression. (PMID:41735305)

Colorectal cancer and immune resistance

  • In an immune-resistant colorectal cancer organoid fraction, B7-H3 expression was significantly elevated, associating it with resistance-associated tumor states. (PMID:41920069)
  • B7-H3 is linked to colorectal cancer as both an associated marker and a diagnostic/prognostic/predictive exosome biomarker. (PMID:41920069; PMID:41964005)
  • The organoid-immunity platform study suggests B7-H3 may help identify metabolic adaptations underlying tumor immune resistance. (PMID:41920069)

Exosomes, tumor microenvironment, and biomarker potential

  • A 2026 Cell Communication and Signaling review (PMID:41964005) described B7-H3 as enriched in exosomes and involved in exosome biogenesis, signaling, and tumor progression. (PMID:41964005)
  • B7-H3-enriched exosomes were reported to modulate the tumor microenvironment to promote immune evasion, metastasis, and therapy resistance. (PMID:41964005)
  • These exosomes show promise as diagnostic, prognostic, and predictive biomarkers in colorectal cancer, non-small cell lung cancer, and prostate cancer. (PMID:41964005)

Pediatric solid tumors and next-generation therapeutics

  • A 2026 Cancer Immunology, Immunotherapy review (PMID:41984108) identified B7-H3 as a tumor-associated antigen targeted by next-generation antibody-drug conjugates in pediatric solid tumors. (PMID:41984108)
  • The same review also highlighted bispecific T cell engagers directed at B7-H3 as part of multimodal immunotherapy strategies. (PMID:41984108)
  • These approaches reflect growing interest in B7-H3 as a broadly applicable target across difficult-to-treat solid tumors. (PMID:41984108)

Signaling pathways

  • B7-H3 activates PI3K pathways, consistent with pro-survival and pro-growth signaling.
  • B7-H3 activates STAT3 pathways, further supporting its role in tumor-promoting signaling networks.