ArticleThe Journal of biological chemistry2015
Humanized Affinity-matured Monoclonal Antibody 8H9 Has Potent Antitumor Activity and Binds to FG Loop of Tumor Antigen B7-H3.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 112 citations in OpenAlex.
- Article
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- EfficientInternational journal of molecular sciences · 2026Article
- From Classical to Emerging Biomarkers of Brain and Central Nervous System Tumors. An Evidence-Based Review with a Focus on Gliomas.Cellular and molecular neurobiology · 2026Review
- B7-H3 (CD276): an actionable therapeutic target and prognostic biomarker across human malignancies.Frontiers in immunology · 2026Review
- Parallel processing of T cells and natural killer cells to enhanceClinical & translational immunology · 2026Article
- Luteolin enhances antitumor immunity of B7-H3-targeted bispecific natural killer cell engagers against non-small cell lung cancer.International journal of biological sciences · 2026Article
- B7-H3 molecular imaging for the era of pan-cancer targeted therapy.Frontiers in pharmacology · 2026Review
- Anti-cancer immune priming with β-radioligand therapy using a novel high affinity antibody selectively targeting the 4Ig-Isoform of B7-H3.Theranostics · 2026Article
- Engineered T cells secreting αB7-H3-αCD3 bispecific engagers for enhanced anti-tumor activity against B7-H3 positive multiple myeloma: a novel therapeutic approach.Journal of translational medicine · 2025Article
- Research progress of B7-H3 in malignant tumors.Frontiers in immunology · 2025Review
- Review
- Medulloblastoma: biology and immunotherapy.Frontiers in immunology · 2025Review
- CAR T Cells Engineered to Secrete IFNκ Induce Tumor Ferroptosis via an IFNAR/STAT1/ACSL4 Axis.Cancer immunology research · 2024Article
- Engineered oncolytic virus expressing B7H3-targeting BiTE enhances antitumor T-cell immune response.Journal for immunotherapy of cancer · 2024Article
- Development of a Human B7-H3-Specific Antibody with Activity against Colorectal Cancer Cells through a Synthetic Nanobody Library.Bioengineering (Basel, Switzerland) · 2024Article
- B7-H3 Inhibitors in Oncology Clinical Trials: A Review.Journal of immunotherapy and precision oncology · 2024Review
- Targeting Histone 3 Variants Epigenetic Landscape and Inhibitory Immune Checkpoints: An Option for Paediatric Brain Tumours Therapy.Current neuropharmacology · 2024Review
- From standard therapies to monoclonal antibodies and immune checkpoint inhibitors - an update for reconstructive surgeons on common oncological cases.Frontiers in immunology · 2024Review
- Patient-derived bladder cancer organoid model to predict sensitivity and feasibility of tailored precision therapy.Current urology · 2023Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
B7-H3 (CD276) is both an inhibitory ligand for natural killer cells and T cells and a tumor antigen that is widely expressed among human solid tumors. Anti-B7-H3 mouse monoclonal antibody 8H9 has been successfully used for radioimmunotherapy for patients with B7-H3(+) tumors. We present the humanization, affinity maturation, and epitope mapping of 8H9 based on structure determination, modeling, and yeast display methods. The crystal structure of ch8H9 Fab fragment was solved to 2.5-Å resolution and used as a template for humanization. By displaying the humanized 8H9 single chain Fv (scFv) on the surface of yeast, the affinity was matured by sequential random mutagenesis and fluorescence-activated cell sorting. Six mutations (three in the complementarity-determining region and three in the framework regions) were identified and incorporated into an affinity-matured humanized 8H9 construct (hu8H9-6m) and an affinity-matured chimeric 8H9 construct (ch8H9-6m). The hu8H9-6m scFv had a 160-fold improvement in affinity (0.9 nm KD) compared with parental hu8H9 scFv (144 nm KD). The IgG formats of ch8H9-6m and hu8H9-6m (nanomolar to subnanomolar KD) had 2-9-fold enhancements in affinity compared with their parental forms, potent in vitro antibody-dependent cell-mediated cytotoxicity (0.1-0.3 μg/ml EC50), and high tumor uptake in mouse xenografts. Based on in silico docking studies and experimental validation, the molecular epitope of 8H9 was determined to be dependent on the FG loop of B7-H3, a region critical to its function in immunologic blockade and unique among anti-B7-H3 antibodies published to date.
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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.