ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Tumor Regression and Delayed Onset Toxicity Following B7-H4 CAR T Cell Therapy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The trial behind it
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Who cites it
32 citing papers in PubMed, 56 citations in OpenAlex.
- Pathology associated with human CAR T cell administration in NOD.Cg-Veterinary pathology · 2026Article
- B7-H4: a multifaceted immune checkpoint and oncoprotein in cancer biology and immunotherapy.Frontiers in immunology · 2026Review
- A Novel B7-H4xCD3 Bispecific T-cell Engager (PF-07260437) Synergizes with Breast Cancer Standard of Care and Immune Checkpoint Therapies.Molecular cancer therapeutics · 2025Article
- Innovative approaches to CAR-T cell therapy: the role of lipid metabolism pathways.Journal of translational medicine · 2025Review
- Exploring B7-H4's Role in Prostate Cancer Dormancy after Androgen Deprivation Therapy: Extracellular Matrix Interactions and Therapeutic Opportunities.Molecular cancer research : MCR · 2025Article
- B7H4 Role in Solid Cancers: A Review of the Literature.Cancers · 2024Review
- CAR-macrophage versus CAR-T for solid tumors: The race between a rising star and a superstar.Biomolecules & biomedicine · 2024Review
- Evaluation of the safety and efficiency of cytotoxic T cell therapy sensitized by tumor antigens original from T-ALL-iPSC in vivo.Cancer innovation · 2024Article
- The role of B7-H4 in ovarian cancer immunotherapy: current status, challenges, and perspectives.Frontiers in immunology · 2024Review
- Discovery and Preclinical Characterization of XMT-1660, an Optimized B7-H4-Targeted Antibody-Drug Conjugate for the Treatment of Cancer.Molecular cancer therapeutics · 2023Article
- Article
- Review
- Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours.Nature reviews. Clinical oncology · 2023Review
- Immune checkpoints and cancer immunotherapies: insights into newly potential receptors and ligands.Therapeutic advances in vaccines and immunotherapy · 2023Review
- B7 Family Members in Pancreatic Ductal Adenocarcinoma: Attractive Targets for Cancer Immunotherapy.International journal of molecular sciences · 2022Review
- Pre-clinical efficacy of CD20-targeted chimeric antigen receptor T cells for non-Hodgkin's lymphoma.Discover oncology · 2022Article
- The immune checkpoint B7x expands tumor-infiltrating Tregs and promotes resistance to anti-CTLA-4 therapy.Nature communications · 2022Article
- Novel immune scoring dynamic nomograms based on B7-H3, B7-H4, and HHLA2: Potential prediction in survival and immunotherapeutic efficacy for gallbladder cancer.Frontiers in immunology · 2022Article
- Role of B7 family members in glioma: Promising new targets for tumor immunotherapy.Frontiers in oncology · 2022Review
- Depleting Tumor Cells Expressing Immune Checkpoint Ligands-A New Approach to Combat Cancer.Cells · 2021Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
B7-H4 protein is frequently overexpressed in ovarian cancer. Here, we engineered T cells with novel B7-H4-specific chimeric antigen receptors (CARs) that recognized both human and murine B7-H4 to test the hypothesis that B7-H4 CAR T cell therapy can be applied safely in preclinical models. B7-H4 CAR T cells specifically secreted IFN-γ and lysed B7-H4(+) targets. In vivo, B7-H4 CAR T cells displayed antitumor reactivity against B7-H4(+) human ovarian tumor xenografts. Unexpectedly, B7-H4 CAR T cell treatment reproducibly showed delayed, lethal toxicity 6-8 weeks after therapy. Comprehensive assessment of murine B7-H4 protein distribution uncovered expression in ductal and mucosal epithelial cells in normal tissues. Postmortem analysis revealed the presence of widespread histologic lesions that correlated with B7-H4(+) expression, and were inconsistent with graft versus host disease. Lastly, expression patterns of B7-H4 protein in normal human tissue were comparable to distribution in mice, advancing our understanding of B7-H4. We conclude that B7-H4 CAR therapy mediates control of cancer outgrowth. However, long-term engraftment of B7-H4 CAR T cells mediates lethal, off-tumor toxicity that is likely due to wide expression of B7-H4 in healthy mouse organs. This model system provides a unique opportunity for preclinical evaluation of safety approaches that limit CAR-mediated toxicity after tumor destruction in vivo.
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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.