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B7-H3 is an immune checkpoint-like surface protein found on 60 to 70% of small-cell lung cancers and 80 to 90% of castration-resistant prostate cancers, with little on normal tissue. It is used as an ADC address, chiefly by ifinatamab deruxtecan, now in phase 3 in small-cell lung cancer; whether blocking its immune-dampening role adds anything beyond payload delivery is unresolved.
B7-H3 (CD276) is an immune checkpoint-like molecule broadly overexpressed in solid tumours with limited normal expression; its function is debated, inhibiting T-cell activation and promoting tumour cell migration. Expression is more homogeneous than many ADC targets, found in 60-70% of small-cell lung cancer and 80-90% of castration-resistant prostate cancer by IHC, as well as head and neck and paediatric solid tumours. Ifinatamab deruxtecan (I-DXd) has shown high response rates in small-cell lung cancer and is in phase 3. B7-H3 is also pursued with radioligands and CAR-T. Whether its immune-dampening role means antibodies against it add an immunological benefit beyond payload delivery is unresolved. The simple version is a widely present tumour surface protein now used mainly as an address for ADCs.
In plain words · B7-H3 is an immune checkpoint-like surface protein found on 60 to 70% of small-cell lung cancers and 80 to 90% of castration-resistant prostate cancers, with little on normal tissue. It is used as an ADC address, chiefly by ifinatamab deruxtecan, now in phase 3 in small-cell lung cancer; whether blocking its immune-dampening role adds anything beyond payload delivery is unresolved.
B7-H3 is an immune checkpoint-like surface protein found on 60 to 70% of small-cell lung cancers and 80 to 90% of castration-resistant prostate cancers, with little on normal tissue. It is used as an ADC address, chiefly by ifinatamab deruxtecan, now in phase 3 in small-cell lung cancer; whether blocking its immune-dampening role adds anything beyond payload delivery is unresolved.
Function debated: inhibits T-cell activation, promotes tumour cell migration. Expression is more homogeneous than many ADC targets.
5 products aim at B7-H3: antibody-drug conjugates and cell therapies. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
Pivotal phase 3 for the B7-H3 ADC from the Merck and Daiichi Sankyo collaboration. Timing is a registry-based estimate. Source
Tumour-associated overexpression: 5 cell-killing or cell-finding medicines (YL201, QLC5508, BNT324 and more) aim at the antigen, which HPA finds stained high in 1 normal tissue; the medicine relies on the tumour carrying more of it than the normal tissue it shares it with. HPA CD276: RNA low tissue specificity; high antibody staining in 1 normal tissue; highest cancer staining skin cancer (7 of 12 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lung cancer (all types), Prostate cancer); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 5 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas CD276 tissue; Human Protein Atlas CD276 pathology; Open Targets ENSG00000103855 associations
First described 2001. Earliest sequence paper UniProt cites for the protein: Chapoval A.I. et al, Nat. Immunol, 2001, "B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Function debated: inhibits T-cell activation, promotes tumour cell migration. Expression is more homogeneous than many ADC targets.
RNA: low tissue specificity, detected in many normal tissues.
Medium: Adipose tissue, Adrenal gland, Appendix, Breast, Bronchus, Cervix, Colon, Duodenum.
Medium only: cervical cancer, colorectal cancer, liver cancer, testis cancer.
HPA CD276 tissue · HPA CD276 pathology · HPA protein class: CD markers
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Prostate cancer | 80-90% | IHC, any expression | Castration-resistant disease | Wikipedia |
| Small-cell lung cancer | 60-70% | IHC, any expression | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
BCB-276 is an experimental CAR-T cell therapy from BrainChild Bio in phase 2 trials for glioma & glioblastoma, aimed at B7-H3.
BNT324 is an experimental antibody-drug conjugate from BioNTech SE in phase 3 trials for prostate cancer and non-small-cell lung cancer, aimed at B7-H3.
Ifinatamab deruxtecan is a B7-H3 ADC showing some of the best response rates ever seen in relapsed small-cell lung cancer.
QLC5508 is an experimental antibody-drug conjugate from Qilu Pharmaceutical in phase 3 trials for oesophageal cancer, prostate cancer and non-small-cell lung cancer, aimed at B7-H3.
YL201 is an experimental antibody-drug conjugate from MediLink Therapeutics (Suzhou) in phase 3 trials for nasopharyngeal carcinoma, non-small-cell lung cancer and small-cell lung cancer, aimed at B7-H3.
Query for this target: (TITLE:"B7-H3" OR ABSTRACT:"B7-H3" OR TITLE:"CD276" OR ABSTRACT:"CD276") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about B7-H3, not a curated reading list.
Shares Aktis Oncology, Overexpression, Bispecific ADC, Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Re-map the tumour's surface proteins before choosing the next antibody drug, Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.