ArticleNature medicine2022
PSMA-targeting TGFβ-insensitive armored CAR T cells in metastatic castration-resistant prostate cancer: a phase 1 trial.
Article in Nature medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03089203 (Phase I Study of CART-PSMA-TGFβRDN Cells in Patients With Advanced Castrate Resistant Prostate Cancer), which is not on this map. Cited by 364 papers, 5 of them syntheses that pooled it.
What it found
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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.
Phase I Study of CART-PSMA-TGFβRDN Cells in Patients With Advanced Castrate Resistant Prostate Cancer
Who cites it
364 citing papers in PubMed, 5 syntheses or guidelines pooled it, 471 citations in OpenAlex.
- Clinical Benefit and Safety of Combined Immunotherapy and Targeted Therapy in Prostate Cancer.International journal of cancer · 2026Pooled it
- Immunotherapeutic strategies for castration-resistant prostate cancer: A systematic review of mechanisms, clinical advances and emerging approaches.Molecular biology reports · 2026Pooled it
- Mapping the clinical landscape of multifunctional CAR T cells: Targets, trends, and synergies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Pooled it
- Prostate cancer and CAR-T therapy: a systematic review.BMC cancer · 2026Pooled it
- The safety and efficacy of chimeric antigen receptor-T cell therapy in solid malignancies: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- Tumor‑immune spatiotemporal co‑evolution: A new paradigm for understanding and overcoming therapy resistance in metastatic castration‑resistant prostate cancer (Review).International journal of molecular medicine · 2026Review
- Novel immunotherapies for prostate cancer.Urologic oncology · 2026Review
- Recent advancements and persisting challenges in the evolution of next generation car t cell therapy for solid malignancies: a comprehensive review.Immunologic research · 2026Review
- PLP1-triggered NOT gate to address neurotoxicity risk of PSMA-targeted prostate cancer therapy.Journal for immunotherapy of cancer · 2026Article
- Barriers and Blueprints: Next-Generation Engineering Strategies for CAR-T Cell Therapy in Gastrointestinal Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- A review of genetic modification for ex vivo cellular therapies.Transfusion · 2026Article
- 177 Lu-PSMA for prostate cancer: progress, challenges and future perspectives.Asian journal of andrology · 2026Review
- Article
- STEAP1-targeted strategies in advanced prostate cancer: a review on therapeutic and diagnostic implications.Prostate cancer and prostatic diseases · 2026Review
- CAR-T cell therapy: potential for paediatric brain tumours-an update.Journal of neuro-oncology · 2026Review
- Piggybacking toward Progress for CAR T-Cell Therapy in Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Article
- CAR T cell therapy beyond cancer: current status, challenges and future prospects.Signal transduction and targeted therapy · 2026Review
- Guanylyl Cyclase 2C-Targeted Chimeric Antigen Receptor T-Cell Therapy in Patients With Metastatic Colorectal Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026Article
- Novel PSCA-Targeting Adapter Molecules for Late-Stage RevCAR-T Cell Therapy in Prostate Cancer.International journal of molecular sciences · 2026Article
304 more citing papers are in PubMed but not listed here.
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Authors and funding
41 authors at 5 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptor (CAR) T cells have demonstrated promising efficacy, particularly in hematologic malignancies. One challenge regarding CAR T cells in solid tumors is the immunosuppressive tumor microenvironment (TME), characterized by high levels of multiple inhibitory factors, including transforming growth factor (TGF)-β. We report results from an in-human phase 1 trial of castration-resistant, prostate cancer-directed CAR T cells armored with a dominant-negative TGF-β receptor (NCT03089203). Primary endpoints were safety and feasibility, while secondary objectives included assessment of CAR T cell distribution, bioactivity and disease response. All prespecified endpoints were met. Eighteen patients enrolled, and 13 subjects received therapy across four dose levels. Five of the 13 patients developed grade ≥2 cytokine release syndrome (CRS), including one patient who experienced a marked clonal CAR T cell expansion, >98% reduction in prostate-specific antigen (PSA) and death following grade 4 CRS with concurrent sepsis. Acute increases in inflammatory cytokines correlated with manageable high-grade CRS events. Three additional patients achieved a PSA reduction of ≥30%, with CAR T cell failure accompanied by upregulation of multiple TME-localized inhibitory molecules following adoptive cell transfer. CAR T cell kinetics revealed expansion in blood and tumor trafficking. Thus, clinical application of TGF-β-resistant CAR T cells is feasible and generally safe. Future studies should use superior multipronged approaches against the TME to improve outcomes.
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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.