ArticleOncoimmunology2016
Transgenic antigen-specific, HLA-A*02:01-allo-restricted cytotoxic T cells recognize tumor-associated target antigen STEAP1 with high specificity.
Article in Oncoimmunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.Experimental hematology & oncology · 2026Review
- Armoring STEAP1 CAR T cells with IL-18 potentiates antitumor activity in Ewing sarcoma.bioRxiv : the preprint server for biology · 2025Article
- Single-Cell RNA Sequencing of Ewing Sarcoma Tumors Demonstrates Transcriptional Heterogeneity and Clonal Evolution.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Vaccines for cancer prevention: exploring opportunities and navigating challenges.Nature reviews. Drug discovery · 2025Review
- Comparative Evaluation of STEAP1 Targeting Chimeric Antigen Receptors with Different Costimulatory Domains and Spacers.International journal of molecular sciences · 2024Article
- Cytokine screening identifies TNF to potentially enhance immunogenicity of pediatric sarcomas.Frontiers in immunology · 2024Article
- TCR-transgenic T cells and YB-1-based oncolytic virotherapy improve survival in a preclinical Ewing sarcoma xenograft mouse model.Frontiers in immunology · 2024Article
- The screening, identification, design and clinical application of tumor-specific neoantigens for TCR-T cells.Molecular cancer · 2023Review
- Targeted Therapy for EWS-FLI1 in Ewing Sarcoma.Cancers · 2023Review
- Shifting from a Biological-Agnostic Approach to a Molecular-Driven Strategy in Rare Cancers: Ewing Sarcoma Archetype.Biomedicines · 2023Review
- Targeting STEAP1 as an anticancer strategy.Frontiers in oncology · 2023Review
- Article
- The Prognostic Value and Immunological Role of STEAP1 in Pan-Cancer: A Result of Data-Based Analysis.Oxidative medicine and cellular longevity · 2022Article
- Article
- Ewing Sarcoma-Derived Extracellular Vesicles Impair Dendritic Cell Maturation and Function.Cells · 2021Article
- Role of immunotherapy in Ewing sarcoma.Journal for immunotherapy of cancer · 2020Review
- Cryo-electron microscopy structure and potential enzymatic function of human six-transmembrane epithelial antigen of the prostate 1 (STEAP1).The Journal of biological chemistry · 2020Article
- MHC Class I-Restricted TCR-Transgenic CD4Cells · 2020Article
- Review
- T cell infiltration into Ewing sarcomas is associated with local expression of immune-inhibitory HLA-G.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pediatric cancers, including Ewing sarcoma (ES), are only weakly immunogenic and the tumor-patients' immune system often is devoid of effector T cells for tumor elimination. Based on expression profiling technology, targetable tumor-associated antigens (TAA) are identified and exploited for engineered T-cell therapy. Here, the specific recognition and lytic potential of transgenic allo-restricted CD8(+) T cells, directed against the ES-associated antigen 6-transmembrane epithelial antigen of the prostate 1 (STEAP1), was examined. Following repetitive STEAP1(130) peptide-driven stimulations with HLA-A*02:01(+) dendritic cells (DC), allo-restricted HLA-A*02:01(-) CD8(+) T cells were sorted with HLA-A*02:01/peptide multimers and expanded by limiting dilution. After functional analysis of suitable T cell clones via ELISpot, flow cytometry and xCELLigence assay, T cell receptors' (TCR) α- and β-chains were identified, cloned into retroviral vectors, codon optimized, transfected into HLA-A*02:01(-) primary T cell populations and tested again for specificity and lytic capacity in vitro and in a Rag2(-/-)γc(-/-) mouse model. Initially generated transgenic T cells specifically recognized STEAP1(130)-pulsed or transfected cells in the context of HLA-A*02:01 with minimal cross-reactivity as determined by specific interferon-γ (IFNγ) release, lysed cells and inhibited growth of HLA-A*02:01(+) ES lines more effectively than HLA-A*02:01(-) ES lines. In vivo tumor growth was inhibited more effectively with transgenic STEAP1(130)-specific T cells than with unspecific T cells. Our results identify TCRs capable of recognizing and inhibiting growth of STEAP1-expressing HLA-A*02:01(+) ES cells in vitro and in vivo in a highly restricted manner. As STEAP1 is overexpressed in a wide variety of cancers, we anticipate these STEAP1-specific TCRs to be potentially useful for immunotherapy of other STEAP1-expressing tumors.
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