Immunotherapeutic targeting of NY-ESO-1 in malignant meningiomas with TCR-transduced T-cells.
| Title: | Immunotherapeutic targeting of NY-ESO-1 in malignant meningiomas with TCR-transduced T-cells. |
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| Authors: | Sun MZ; University of Texas Southwestern School of Medicine, 5323 Harry Hines Blvd Mail Ext Code: 8855, Dallas, TX, 75390, USA. Matthew.sun@utsouthwestern.edu.; University of California Los Angeles, 300 Stein Plaza Driveway Suite 420, Los Angeles, CA, 90095, USA. Matthew.sun@utsouthwestern.edu.; Contreras E; University of California Los Angeles, 300 Stein Plaza Driveway Suite 420, Los Angeles, CA, 90095, USA.; Treger J; University of California Los Angeles, 300 Stein Plaza Driveway Suite 420, Los Angeles, CA, 90095, USA.; Imbroane M; University of California Los Angeles, 300 Stein Plaza Driveway Suite 420, Los Angeles, CA, 90095, USA.; Orpilla J; University of California Los Angeles, 300 Stein Plaza Driveway Suite 420, Los Angeles, CA, 90095, USA.; Ko M; University of California Los Angeles, 300 Stein Plaza Driveway Suite 420, Los Angeles, CA, 90095, USA.; Reynoso J; University of California Los Angeles, 300 Stein Plaza Driveway Suite 420, Los Angeles, CA, 90095, USA.; Khattab S; University of California Los Angeles, 300 Stein Plaza Driveway Suite 420, Los Angeles, CA, 90095, USA.; Lai TJ; University of California Los Angeles, 300 Stein Plaza Driveway Suite 420, Los Angeles, CA, 90095, USA.; Tsang JE; University of California Los Angeles, 300 Stein Plaza Driveway Suite 420, Los Angeles, CA, 90095, USA.; Vitte J; University of California Los Angeles, 300 Stein Plaza Driveway Suite 420, Los Angeles, CA, 90095, USA.; Giovannini M; University of California Los Angeles, 300 Stein Plaza Driveway Suite 420, Los Angeles, CA, 90095, USA.; Liau LM; University of California Los Angeles, 300 Stein Plaza Driveway Suite 420, Los Angeles, CA, 90095, USA.; Prins R; University of California Los Angeles, 300 Stein Plaza Driveway Suite 420, Los Angeles, CA, 90095, USA.; Everson RG; University of California Los Angeles, 300 Stein Plaza Driveway Suite 420, Los Angeles, CA, 90095, USA. REverson@mednet.ucla.edu. |
| Source: | Journal of neuro-oncology [J Neurooncol] 2025 Dec; Vol. 175 (3), pp. 1079-1089. Date of Electronic Publication: 2025 Aug 13. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Springer Country of Publication: United States NLM ID: 8309335 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-7373 (Electronic) Linking ISSN: 0167594X NLM ISO Abbreviation: J Neurooncol Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2005- : New York : Springer; Original Publication: Boston : M. Nijhoff, 1983- |
| MeSH Terms: | Meningioma*/therapy ; Meningioma*/immunology ; Meningioma*/pathology ; Meningioma*/metabolism ; Membrane Proteins*/metabolism ; Membrane Proteins*/immunology ; Meningeal Neoplasms*/therapy ; Meningeal Neoplasms*/immunology ; Meningeal Neoplasms*/pathology ; Meningeal Neoplasms*/metabolism ; T-Lymphocytes*/immunology ; T-Lymphocytes*/metabolism ; T-Lymphocytes*/transplantation ; Receptors, Antigen, T-Cell*/metabolism ; Receptors, Antigen, T-Cell*/genetics ; Receptors, Antigen, T-Cell*/immunology ; Antigens, Neoplasm*/metabolism ; Antigens, Neoplasm*/immunology ; Immunotherapy, Adoptive*/methods; Animals ; Humans ; Mice ; Female ; Male ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; Xenograft Model Antitumor Assays ; Aged ; Tumor Cells, Cultured ; Cell Line, Tumor ; Coculture Techniques |
| Abstract: | Introduction: Malignant meningiomas lack effective immunotherapeutic options. NY-ESO-1 is a potential immunotherapeutic target, because it is the most frequently expressed cancer-testis-antigen in meningiomas. We investigated the efficacy of T-Cell-Receptor-Transduced T-Cells (TCR-T) targeting NY-ESO-1 in vitro and in vivo in meningiomas.; Methods: Immunohistochemistry was performed on Grade I-III meningioma specimens. Primary meningioma culture LB3750(Grade I) and immortalized cultures SF1335(Grade I) and CH157-HLA-A2.1(Grade III) were established and maintained in vitro. NY-ESO-1 TCR-T (HLA-A2.1 restricted) cells were co-cultured with primary and immortalized meningioma cells and assessed for real-time tumor killing in vitro. Immunodeficient NSG mice were intracranially implanted with CH157-HLA-A2.1 and SF1335 cells, treated with systemic adoptive cell transfer (ACT) of TCR-T, and assessed for overall survival in vivo.; Results: NY-ESO-1 expression correlated with tumor grade (n = 35; p 60% and then nearly 100% cytolysis after co-culture with TCR-T for 10 and 24 h, respectively, compared with control T-cells (p |
| Competing Interests: | Declarations. Competing interests: The authors declare no competing interests. |
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| Grant Information: | P50CA211015 CEP United States NH NIH HHS; NS079198 United States NH NIH HHS |
| Contributed Indexing: | Keywords: Meningioma immunotherapy; NY-ESO-1; Systemic adoptive cell transfer; TCR-T; Local Abstract: [Publisher, French] No effective immunotherapy exists for malignant meningioma. NY-ESO-1 is widely expressed in meningiomas but not in normal cells, making it an ideal immunotherapeutic target. Engineered T cells have been used to target NY-ESO-1 in melanomas and sarcomas but not in brain tumors. We found that T cells targeting NY-ESO-1 effectively killed meningiomas in vitro, with the efficacy correlating with tumor NY-ESO-1 expression. Adoptive cell transfer of these T cells results in significantly increased survival in vivo in high-grade meningiomas. Our study demonstrated that targeting NY-ESO-1 with T cells may be a clinically feasible adjuvant immunotherapeutic strategy for treating high-grade meningiomas. |
| Substance Nomenclature: | 0 (CTAG1B protein, human); 0 (Membrane Proteins); 0 (Receptors, Antigen, T-Cell); 0 (Antigens, Neoplasm) |
| Entry Date(s): | Date Created: 20250813 Date Completed: 20251009 Latest Revision: 20260311 |
| Update Code: | 20260311 |
| DOI: | 10.1007/s11060-025-05200-z |
| PMID: | 40802116 |
| Database: | MEDLINE |
Journal Article