ArticleThe Journal of clinical investigation2023
Antitumor activity of AZD0754, a dnTGFβRII-armored, STEAP2-targeted CAR-T cell therapy, in prostate cancer.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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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.
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Who cites it
37 citing papers in PubMed, 42 citations in OpenAlex.
- 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
- Real-world pharmacovigilance signals of antibody-drug conjugates: reporting patterns by payload, linker, target, and sex in FAERS.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The RNA cargo of plasma-derived extracellular vesicles in mCRPC patients captures cancer cells and tumor microenvironment signals.bioRxiv : the preprint server for biology · 2026Article
- Recent advances in molecular mechanisms to improve the efficacy of CAR-T cell therapy for viral diseases, cancer, and autoimmune diseases.Stem cell research & therapy · 2026Review
- A review of genetic modification for ex vivo cellular therapies.Transfusion · 2026Article
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- Nanomedicine in immunotherapy of urinary system tumors: advances, synergistic strategies, and translational challenges.Journal of nanobiotechnology · 2026Review
- Nanobody-Engineered CLL-1 CAR T Cells: Optimizing Tumor-Specific Cytotoxicity and Minimizing Off-Tumor Toxicity.Cancer research communications · 2026Article
- Targeting urological cancers with CAR-T cell therapy: current landscape and future directions.Journal of translational medicine · 2026Review
- Characteristics and therapeutic resistance mechanisms of the prostate cancer immune microenvironment: a comprehensive analysis from bench to clinic.Frontiers in pharmacology · 2026Review
- Engineering a juxtamembrane-targeting CAR T-cell against mesothelin: a novel binder resilient to shed antigen for enhanced efficacy against ovarian and pancreatic cancer.Frontiers in immunology · 2026Article
- Harnessing the immune system: future directions in cancer immunotherapy.Frontiers in immunology · 2026Review
- Mechanisms of resistance to antibody-drug conjugates in cancer: molecular barriers and pharmacological solutions.Cancer chemotherapy and pharmacology · 2025Review
- Tumor microenvironment-mediated immune evasion and resistance in prostate cancer: mechanisms, cross-talk, and therapeutic opportunities.Clinical and experimental medicine · 2025Review
- The evolving landscape of antibody-drug conjugates (ADCs) for treatment of prostate cancer.NPJ precision oncology · 2025Review
- CAR-T Cell Therapy for Prostate Cancer: Current Advances and Future Perspectives.Biomedicines · 2025Review
- Synergistic targeting strategies for prostate cancer.Nature reviews. Urology · 2025Review
- The mechanisms and clinical significance of CD8Cancer biology & medicine · 2025Review
Corrections and comments
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Authors and funding
29 authors at 5 institutions in 8 countries.
Funding
Abstract
Prostate cancer is generally considered an immunologically "cold" tumor type that is insensitive to immunotherapy. Targeting surface antigens on tumors through cellular therapy can induce a potent antitumor immune response to "heat up" the tumor microenvironment. However, many antigens expressed on prostate tumor cells are also found on normal tissues, potentially causing on-target, off-tumor toxicities and a suboptimal therapeutic index. Our studies revealed that six-transmembrane epithelial antigen of prostate-2 (STEAP2) was a prevalent prostate cancer antigen that displayed high, homogeneous cell surface expression across all stages of disease with limited distal normal tissue expression, making it ideal for therapeutic targeting. A multifaceted lead generation approach enabled development of an armored STEAP2 chimeric antigen receptor T cell (CAR-T) therapeutic candidate, AZD0754. This CAR-T product was armored with a dominant-negative TGF-β type II receptor, bolstering its activity in the TGF-β-rich immunosuppressive environment of prostate cancer. AZD0754 demonstrated potent and specific cytotoxicity against antigen-expressing cells in vitro despite TGF-β-rich conditions. Further, AZD0754 enforced robust, dose-dependent in vivo efficacy in STEAP2-expressing cancer cell line-derived and patient-derived xenograft mouse models, and exhibited encouraging preclinical safety. Together, these data underscore the therapeutic tractability of STEAP2 in prostate cancer as well as build confidence in the specificity, potency, and tolerability of this potentially first-in-class CAR-T therapy.
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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.