B7-H3 Targeting in Cancer Immunotherapy

B7-H3 (CD276) is an immune checkpoint molecule aberrantly overexpressed on a wide range of tumour cells and associated stromal elements, while showing limited distribution in normal tissues. Its dual role in suppressing antitumour T-cell function and promoting non-immunological processes such as proliferation, angiogenesis, metastasis and therapeutic resistance makes it an attractive target for precision immunotherapy. Strategies to exploit B7-H3 include monoclonal antibodies, antibody–drug conjugates, bispecific T-cell engagers and chimeric antigen receptor (CAR) T-cell therapies, all designed to deliver cytotoxic payloads or redirect effector lymphocytes selectively to B7-H3-positive malignancies. In parallel, the development of noninvasive imaging agents targeting B7-H3 promises to guide patient selection, assess target engagement and monitor response or the emergence of resistance. Collectively, these approaches underscore the global significance of B7-H3 blockade and illustrate its potential to enhance efficacy while minimising off-target toxicity.

Research from Nature Portfolio

Recent studies have elucidated key regulators of B7-H3 expression and function in human cancers. Investigations into mechanistic target of rapamycin complex 1 (mTORC1) signalling have demonstrated that mTORC1 activity drives transcriptional upregulation of B7-H3 via phosphorylation of specific transcription factors, leading to suppression of cytotoxic CD4+ T-cell subsets and worse clinical outcomes. Inhibition of B7-H3 in mTORC1-hyperactive tumours restores T-cell infiltration, enhances interferon-γ responses and suppresses tumour growth. Earlier foundational work revealed that soluble forms of B7-H3 promote invasion and metastasis in pancreatic carcinoma through engagement of Toll-like receptor 4 (TLR4) and activation of the NF-κB pathway, establishing a paradigm for how B7-H3 can mediate both immune evasion and direct oncogenic signalling.

B7-H3 Targeting in Cancer Immunotherapy publication trend

The graph below shows the total number of articles in b7-h3 targeting in cancer immunotherapy across all publications each year (not limited to Nature Index journals).

Technical terms

Immune checkpoint: A regulator of immune activation that can inhibit T-cell responses and is exploited by tumours to evade immunity.

mTORC1: A signalling complex that controls cell growth and metabolism in response to nutrients and growth factors.

Bispecific antibody: An engineered antibody capable of binding two different antigens or epitopes simultaneously to direct immune cells to targets.

Tumour microenvironment (TME): The complex milieu of cells, molecules and blood vessels surrounding a tumour that influences its growth and immune interactions.

NF-κB pathway: A signalling cascade that regulates inflammation, cell survival and gene expression in immune responses and cancer.

Toll-like receptor 4 (TLR4): A membrane receptor that recognises pathogen-associated patterns and activates inflammatory signalling.

References

1. New frontiers in immune checkpoint B7-H3 (CD276) research and drug development. Molecular Cancer (2023).
2. mTORC1 upregulates B7-H3/CD276 to inhibit antitumor T cells and drive tumor immune evasion. Nature Communications (2023).
3. Soluble B7-H3 promotes the invasion and metastasis of pancreatic carcinoma cells through the TLR4/NF-κB pathway. Scientific Reports (2016).
4. An optimized IgG-based B7-H3xCD3 bispecific antibody for treatment of gastrointestinal cancers. Molecular Therapy (2023).
5. A whole-body imaging technique for tumor-specific diagnostics and screening of B7-H3-targeted therapies. Journal of Clinical Investigation (2025).