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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.
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.
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.
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.
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.
Immune or microenvironment target: the record's class is immune checkpoint. HPA VTCN1: RNA tissue enhanced (breast 95 nTPM, fallopian tube 31 nTPM, pancreas 28 nTPM); high antibody staining in 2 normal tissues. Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Breast cancer (all types), Ovarian cancer, Endometrial cancer); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 1 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas VTCN1 tissue; UniProt Q7Z7D3; Open Targets ENSG00000134258 associations
First described 2003. Earliest sequence paper UniProt cites for the protein: Sica G.L. et al, Immunity, 2003, "B7-H4, a molecule of the B7 family, negatively regulates T cell immunity". Source.
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.
RNA: tissue enhanced (breast 95 nTPM, fallopian tube 31 nTPM, pancreas 28 nTPM), detected in many normal tissues.
Medium: Adrenal gland, Breast, Colon, Epididymis, Fallopian tube, Gallbladder, Kidney, Seminal vesicle.
RNA group enriched: Breast Invasive Carcinoma 100 pTPM, Ovary Serous Cystadenocarcinoma 78 pTPM, Uterine Corpus Endometrial Carcinoma 88 pTPM.
No cancer stained high; medium in head and neck cancer, pancreatic cancer, stomach cancer.
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.
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.
Puxitatug samrotecan is a B7-H4 ADC targeting a checkpoint-like protein enriched in breast, ovarian, and endometrial cancers.
It explains why a PD-L1 score alone predicts imperfectly: PD-L1 on stromal cells with excluded T cells is a poor-outcome pattern, and B7-H4 marks the cold tumours now being targeted by antibody-drug conjugates.
Independently arrived at the same partition as the refined Lehmann scheme and added the insight that immune activation within basal-like tumours separates longer from shorter survival, the biology immunotherapy would exploit three years later.
Query for this target: (TITLE:"B7-H4" OR ABSTRACT:"B7-H4" OR TITLE:"VTCN1" OR ABSTRACT:"VTCN1" OR TITLE:"B7H4" OR ABSTRACT:"B7H4" OR TITLE:"B7x" OR ABSTRACT:"B7x" OR TITLE:"B7S1" OR ABSTRACT:"B7S1" OR TITLE:"V-set domain containing T cell activation inhibitor 1" OR ABSTRACT:"V-set domain containing T cell activation inhibitor 1") 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-H4 (VTCN1), not a curated reading list.
Shares Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers, Cold tumours: immune deserts and exclusion, Checkpoint (two meanings) and the tag wave5-target.
Shares HHLA2 (B7-H7), Checkpoint (two meanings), PD-1 / PD-L1 immune checkpoint & T-cell activation and the tag wave5-target.
Shares Checkpoint (two meanings), PD-1 / PD-L1 immune checkpoint & T-cell activation and the tag wave5-target.
Shares Checkpoint (two meanings), PD-1 / PD-L1 immune checkpoint & T-cell activation and the tag wave5-target.
Shares PD-1 / PD-L1 immune checkpoint & T-cell activation and the tag wave5-target.
Shares Triple-negative breast cancer (TNBC) and the tag wave5-target.
Shares Ovarian cancer and the tag wave5-target.
Shares HS-20089, Endometrial cancer, Ovarian cancer.