ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
A B7-H4-Targeting Antibody-Drug Conjugate Shows Antitumor Activity in PARPi and Platinum-Resistant Cancers with B7-H4 Expression.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Prognostic Value of B7H4 Expression in Patients with Solid Cancers: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2024Pooled it
- Drug-specific differences in fatal adverse events among PARP inhibitors: a FAERS pharmacovigilance study.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- B7-H4-targeted radiotheranostics enable precise imaging and potent therapy across solid tumor models.Science advances · 2026Article
- Conformational epitope engagement by anti-MSLN ADC RC88 confers resistance to soluble mesothelin.Antibody therapeutics · 2026Article
- Immune Evasion in Ovarian Cancer Peritoneal Metastasis: Mechanisms and Biomarker-Guided Therapeutic Matching.Journal of cellular physiology · 2026Review
- Antibody-Drug Conjugates in Gynecologic Oncology: Advances, Challenges, and Future Directions.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Development and application of antibody-drug conjugates in gynecological cancers.Science China. Life sciences · 2026Review
- Article
- Clinical Significance of B7-H4 in Peripheral Blood of Patients With Myasthenia Gravis.Journal of immunology research · 2026Article
- Antibody-drug conjugates in cancer therapy: current landscape, challenges, and future directions.Molecular cancer · 2025Review
- Palmitoylation modulates antitumor immunity.Molecular biology reports · 2025Review
- Navigating PARP Inhibitor Resistance in Ovarian Cancer: Bridging Mechanistic Insights To Clinical Translation.Current treatment options in oncology · 2025Review
- Elevated tumor NOS2/COX2 promotes immunosuppressive phenotypes associated with poor survival in ER- breast cancer.JCI insight · 2025Article
- Application of Immune Checkpoint Inhibitors in Cancer.MedComm · 2025Review
- Investigation of the Effects of B7H4 (rs10754339 A>G) Gene Polymorphism and Serum Level on Breast Cancer Susceptibility.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Monotherapy and combination therapy using antibody‑drug conjugates for platinum‑resistant ovarian cancer.Oncology reports · 2025Review
- Reprogramming the Tumor Immune Microenvironment with ICAM-1-Targeted Antibody‒Drug Conjugates and B7-H3-CD3 Bispecific Antibodies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Development of Antibody-Drug Conjugates for Malignancies of the Uterine Corpus: A Review.Cells · 2025Review
- sB7-H4 is a diagnostic biomarker in epithelial ovarian cancer and correlates to platinum resistance.Clinical and experimental immunology · 2025Article
- Lung cancer tumor immune microenvironment: analyzing immune escape mechanisms and exploring emerging therapeutic targets.Frontiers in immunology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 3 institutions in 3 countries.
Funding
Abstract
purposePlatinum and PARP inhibitors (PARPi) demonstrate activity in breast and ovarian cancers, but drug resistance ultimately emerges. Here, we examine B7-H4 expression in primary and recurrent high-grade serous ovarian carcinoma (HGSOC) and the activity of a B7-H4-directed antibody-drug conjugate (B7-H4-ADC), using a pyrrolobenzodiazepine-dimer payload, in PARPi- and platinum-resistant HGSOC patient-derived xenograft (PDX) models. EXPERIMENTAL
designB7-H4 expression was quantified by flow cytometry and IHC. B7-H4-ADC efficacy was tested against multiple cell lines in vitro and PDX in vivo. The effect of B7-H4-ADC on cell cycle, DNA damage, and apoptosis was measured using flow cytometry.
resultsB7-H4 is overexpressed in 92% of HGSOC tumors at diagnosis (n = 12), persisted in recurrent matched samples after platinum treatment, and was expressed at similar levels across metastatic sites after acquired multi-drug resistance (n = 4). Treatment with B7-H4-ADC resulted in target-specific growth inhibition of multiple ovarian and breast cancer cell lines. In platinum- or PARPi-resistant ovarian cancer cells, B7-H4-ADC significantly decreased viability and colony formation while increasing cell-cycle arrest and DNA damage, ultimately leading to apoptosis. Single-dose B7-H4-ADC led to tumor regression in 65.5% of breast and ovarian PDX models (n = 29), with reduced activity in B7-H4 low or negative models. In PARPi and platinum-resistant HGSOC PDX models, scheduled B7-H4-ADC dosing led to sustained tumor regression and increased survival.
conclusionsThese data support B7-H4 as an attractive ADC target for treatment of drug-resistant HGSOC and provide evidence for activity of an ADC with a DNA-damaging payload in this population. See related commentary by Veneziani et al., p. 1434.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.