ArticleBlood2009
Lack of specific gamma-retroviral vector long terminal repeat promoter silencing in patients receiving genetically engineered lymphocytes and activation upon lymphocyte restimulation.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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.
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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
43 citing papers in PubMed, 66 citations in OpenAlex.
- T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Trial
- Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2011Trial
- Hallmarks and correlates of effective adoptive cell immunotherapy for cancer.Nature reviews. Immunology · 2026Review
- Regulation of CAR transgene expression to design semiautonomous CAR-T.Molecular therapy. Oncology · 2024Review
- Safety and biological outcomes following a phase 1 trial of GD2-specific CAR-T cells in patients with GD2-positive metastatic melanoma and other solid cancers.Journal for immunotherapy of cancer · 2024Article
- Nonactivated and IL-7 cultured CD19-specific CAR T cells are enriched in stem cell phenotypes and functionally superior.Blood advances · 2024Article
- Targeting TGFβ with chimeric switch receptor and secreted trap to improve T cells anti-tumor activity.Frontiers in immunology · 2024Article
- Host Interactions with Engineered T-cell Micropharmacies.Cancer immunology research · 2023Article
- Host-cell Interactions of Engineered T cell Micropharmacies.bioRxiv : the preprint server for biology · 2023Article
- Engineering CAR-T cells for radiohapten capture in imaging and radioimmunotherapy applications.Theranostics · 2023Article
- HDAC inhibition prevents transgene expression downregulation and loss-of-function in T-cell-receptor-transduced T cells.Molecular therapy oncolytics · 2021Article
- Epigenetic Suppression of Transgenic T-cell Receptor Expression via Gamma-Retroviral Vector Methylation in Adoptive Cell Transfer Therapy.Cancer discovery · 2020Article
- Promoter choice: Who should drive the CAR in T cells?PloS one · 2020Article
- Gene editing: Towards the third generation of adoptive T-cell transfer therapies.Immuno-oncology technology · 2019Review
- Stable and reproducible transgene expression independent of proliferative or differentiated state using BAC TG-EMBED.Gene therapy · 2018Article
- Combination immunotherapies implementing adoptive T-cell transfer for advanced-stage melanoma.Melanoma research · 2018Review
- Fludarabine and neurotoxicity in engineered T-cell therapy.Gene therapy · 2018Article
- Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- CARs: Synthetic Immunoreceptors for Cancer Therapy and Beyond.Trends in molecular medicine · 2017Review
- Current approaches to increase CAR T cell potency in solid tumors: targeting the tumor microenvironment.Journal for immunotherapy of cancer · 2017Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Retroviral transduction of tumor antigen-specific T-cell receptor (TCR) genes into lymphocytes redirects T cells to lyse tumors. Furthermore, adoptive transfer of these lymphocytes has mediated objective responses in patients with metastatic cancer. From 2004 to 2006, more than 40 patients were treated with autologous gene-modified lymphocytes expressing a melanoma antigen-specific TCR at the National Cancer Institute. Eighteen such patients were analyzed for persistence and gene expression in vivo. In addition, the impact of epigenetic silencing and of lymphocyte restimulation was studied. Although gene-modified lymphocytes persisted in vivo, the shutdown of TCR transgene expression was observed. Bisulfite sequencing analysis and ex vivo DNA methyltransferase inhibition demonstrated that the decrease in gene expression did not result from DNA methylation. Surprisingly, down-regulation of vector-driven transgene transcriptional activity was not vector specific but mimicked that of endogenous genes. The decrease in TCR transgene expression, however, was reversed upon lymphocyte stimulation. These data demonstrate a lack of gamma-retroviral promoter-specific gene silencing in adoptively transferred human lymphocytes and support that transgene expression is largely affected by global cellular mechanisms. The use of immunomodulatory adjuvants, eg, vaccination or cytokine therapy, for in vivo T-cell activation may help overcome this metabolic quiescence and thus augment cellular immunotherapy-based cancer 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.