ArticleJournal for immunotherapy of cancer2023
Immunotherapy resistance driven by loss of NY-ESO-1 expression in response to transgenic adoptive cellular therapy with PD-1 blockade.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02775292 (NY-ESO-1 TCR Engineered Adoptive Cell Transfer Therapy With Nivolumab PD-1 Blockade), which is not on this map. Cited by 17 papers.
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.
NY-ESO-1 TCR Engineered Adoptive Cell Transfer Therapy With Nivolumab PD-1 Blockade
Who cites it
17 citing papers in PubMed, 17 citations in OpenAlex.
- Letetresgene Autoleucel in Advanced/Metastatic Myxoid/Round Cell Liposarcoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- The evolution of cellular therapies in sarcoma: Breakthroughs, challenges, and future directions.Human vaccines & immunotherapeutics · 2026Review
- TCR-JANUS engager proteins enable bispecific targeting to overcome tumor heterogeneity in TCR-T cell therapy.Science advances · 2026Article
- Targeting solid tumors with TCR-T cells: mechanisms, progress, and challenges.Frontiers in oncology · 2026Review
- Overcoming immunotherapy barriers in pediatric brain tumors: epigenetic strategies.Frontiers in oncology · 2026Review
- Immunotherapeutic targeting of NY-ESO-1 in malignant meningiomas with TCR-transduced T-cells.Journal of neuro-oncology · 2025Article
- Genetic Heterogeneity of Undifferentiated Pleomorphic Sarcoma: Is There Potential for Targeted Therapy?Cancers · 2025Review
- Immunotherapy in the Treatment of Undifferentiated Pleomorphic Sarcoma and Myxofibrosarcoma.Current treatment options in oncology · 2025Review
- Human cancer-targeted immunity via transgenic hematopoietic stem cell progeny.Nature communications · 2025Article
- Stabilized iRGD modification enhances NY-ESO-1 TCR-T infiltration in solid tumors and synergizes with PD-1 blockade.Cancer immunology, immunotherapy : CII · 2025Article
- Potential Mechanisms for Immunotherapy Resistance in Adult Soft-Tissue Sarcoma.Targeted oncology · 2025Review
- Immunotherapy in Breast Cancer: Beyond Immune Checkpoint Inhibitors.International journal of molecular sciences · 2025Review
- NY-ESO-1 antigen: A promising frontier in cancer immunotherapy.Clinical and translational medicine · 2024Review
- Single-cell sequencing unveils extensive intratumoral heterogeneity of cancer/testis antigen expression in melanoma and lung cancer.Journal for immunotherapy of cancer · 2024Article
- Neoantigen-specific stimulation of tumor-infiltrating lymphocytes enables effective TCR isolation and expansion while preserving stem-like memory phenotypes.Journal for immunotherapy of cancer · 2024Article
- Current knowledge about immunotherapy resistance for melanoma and potential predictive and prognostic biomarkers.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Current advances in cancer vaccines targeting NY-ESO-1 for solid cancer treatment.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe tumor antigen NY-ESO-1 has been shown to be an effective target for transgenic adoptive cell therapy (ACT) for the treatment of sarcoma and melanoma. However, despite frequent early clinical responses, many patients ultimately develop progressive disease. Understanding the mechanisms underlying treatment resistance is crucial to improve future ACT protocols. Here, we describe a novel mechanism of treatment resistance in sarcoma involving loss of expression of NY-ESO-1 in response to transgenic ACT with dendritic cell (DC) vaccination and programmed cell death protein-1 (PD-1) blockade.
methodsA HLA-A*02:01-positive patient with an NY-ESO-1-positive undifferentiated pleomorphic sarcoma was treated with autologous NY-ESO-1-specific T-cell receptor (TCR) transgenic lymphocytes, NY-ESO-1 peptide-pulsed DC vaccination, and nivolumab-mediated PD-1 blockade.
resultsPeripheral blood reconstitution with NY-ESO-1-specific T cells peaked within 2 weeks of ACT, indicating rapid in vivo expansion. There was initial tumor regression, and immunophenotyping of the peripheral transgenic T cells showed a predominantly effector memory phenotype over time. Tracking of transgenic T cells to the tumor sites was demonstrated in on-treatment biopsy via both TCR sequencing-based and RNA sequencing-based immune reconstitution, and nivolumab binding to PD-1 on transgenic T cells was confirmed at the tumor site. At the time of disease progression, the promoter region of NY-ESO-1 was found to be extensively methylated, and tumor NY-ESO-1 expression was completely lost as measured by RNA sequencing and immunohistochemistry.
conclusionsACT of NY-ESO-1 transgenic T cells given with DC vaccination and anti-PD-1 therapy resulted in transient antitumor activity. NY-ESO-1 expression was lost in the post-treatment sample in the setting of extensive methylation of the NY-ESO-1 promoter region. BIOLOGICAL/CLINICAL INSIGHT: Antigen loss represents a novel mechanism of immune escape in sarcoma and a new point of improvement in cellular therapy approaches. TRIAL REGISTRATION NUMBER: NCT02775292.
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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.