B7-H4 (VTCN1)

aka B7-H4, B7H4, B7x, B7S1, V-set domain containing T cell activation inhibitor 1

B7-H4 is a checkpoint-like protein that many breast, ovarian and endometrial tumours carry on their surface. Antibody-drug conjugates such as puxitatug samrotecan and HS-20089 use it as a docking site to deliver a chemotherapy payload.

VTCN1 (chromosome 1p13.1-p12) encodes B7-H4, a ligand that negatively regulates T-cell-mediated immunity by inhibiting T-cell activation, proliferation, cytokine production and the development of cytotoxicity; on tumour macrophages it works with regulatory T cells to suppress tumour-antigen-specific T-cell immunity, and it promotes epithelial cell transformation (UniProt Q7Z7D3). In OnCo it is the surface target of two topoisomerase I payload antibody-drug conjugates: puxitatug samrotecan, in triple-negative breast, ovarian and endometrial cancer, and HS-20089, a humanised IgG1 with a protease-cleavable linker and a drug-to-antibody ratio of about 6, in phase 3 for ovarian and endometrial cancer.

B7-H4 (VTCN1): what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · B7-H4 is a checkpoint-like protein that many breast, ovarian and endometrial tumours carry on their surface. Antibody-drug conjugates such as puxitatug samrotecan and HS-20089 use it as a docking site to deliver a chemotherapy payload.

1 · What it is
B7-H4 is a checkpoint-like protein that many breast, ovarian and endometrial tumours carry on their surface. Antibody-drug conjugates such as puxitatug samrotecan and HS-20089 use it as a docking site to deliver a chemotherapy payload.
2 · What goes wrong in cancer
The puxitatug samrotecan record calls B7-H4 a checkpoint-like protein enriched in breast, ovarian and endometrial cancers; in the corpus it is used as an ADC address rather than as a checkpoint to block.
3 · How drugs use it
2 products aim at B7-H4 (VTCN1): antibody-drug conjugates. Checkpoint drugs are antibodies that cover one side of an immune ‘stand down’ handshake so T cells stay active.

Full dossier: hotspots, trials, resistance, assays, models, open questions →

External identifiers

VTCN1HGNCEnsemblUniProtAlphaFold DBOpen TargetsCIViCOncoKBCOSMICcBioPortalDepMapHuman Protein AtlasNCBI GeneOMIM

Biology

The puxitatug samrotecan record calls B7-H4 a checkpoint-like protein enriched in breast, ovarian and endometrial cancers; in the corpus it is used as an ADC address rather than as a checkpoint to block.

Where it is found

Triple-negative breast cancer
Ovarian and endometrial cancer
Tumour-associated macrophages

Class

checkpoint · VTCN1

Identifiers

HGNC HGNC:28873Ensembl ENSG00000134258UniProt Q7Z7D3NCBI Gene 79679

Products

2top

Phase 3ADC

HS-20089

HS-20089 is an experimental antibody-drug conjugate from Hansoh BioMedical R&D in phase 3 trials for ovarian cancer and endometrial cancer, with its target not yet stated publicly.

Phase 2ADC

Puxitatug samrotecan

Puxitatug samrotecan is a B7-H4 ADC targeting a checkpoint-like protein enriched in breast, ovarian, and endometrial cancers.