ArticleGene therapy2013
The immunogenicity of virus-derived 2A sequences in immunocompetent individuals.
Article in Gene therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Combined Treatment with Autologous CIK Cells, Radiotherapy and Chemotherapy in Advanced Cervical Cancer.Pathology oncology research : POR · 2019Trial
- CAR-mediated release of IL-10 increases the function of regulatory T cells: Relevance for future clinical application.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Recent findings on chimeric antigen receptor (CAR)-engineered immune cell therapy in solid tumors and hematological malignancies.Stem cell research & therapy · 2022Review
- Chimeric antigen receptor-modified human regulatory T cells that constitutively express IL-10 maintain their phenotype and are potently suppressive.European journal of immunology · 2021Article
- Immunogenicity of CAR T cells in cancer therapy.Nature reviews. Clinical oncology · 2021Review
- Efficacy of a Bicistronic Vector for Correction of Sandhoff Disease in a Mouse Model.Molecular therapy. Methods & clinical development · 2019Article
- Reprogramming cellular functions with engineered membrane proteins.Current opinion in biotechnology · 2017Review
- Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes.The Journal of clinical investigation · 2017Article
- Balanced secretion of anti-CEA × anti-CD3 diabody chains using the 2A self-cleaving peptide maximizes diabody assembly and tumor-specific cytotoxicity.Gene therapy · 2017Article
- Inducible Caspase-9 Selectively Modulates the Toxicities of CD19-Specific Chimeric Antigen Receptor-Modified T Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Structures and Corresponding Functions of Five Types of Picornaviral 2A Proteins.Frontiers in microbiology · 2017Review
- Optimized human CYP4B1 in combination with the alkylator prodrug 4-ipomeanol serves as a novel suicide gene system for adoptive T-cell therapies.Gene therapy · 2016Article
- Serial Activation of the Inducible Caspase 9 Safety Switch After Human Stem Cell Transplantation.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Clonal Dynamics In Vivo of Virus Integration Sites of T Cells Expressing a Safety Switch.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Efficient expression of bioactive murine IL12 as a self-processing P2A polypeptide driven by inflammation-regulated promoters in tumor cell lines.Cancer gene therapy · 2015Article
- An Inducible Caspase-9 Suicide Gene to Improve the Safety of Therapy Using Human Induced Pluripotent Stem Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
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- Adoptive T-cell therapy: adverse events and safety switches.Clinical & translational immunology · 2014Review
- Building and optimizing a virus-specific T cell receptor library for targeted immunotherapy in viral infections.Scientific reports · 2014Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Genetic engineering of T cells for adoptive immunotherapy in cancer patients has shown significant promise. To ensure optimal antitumor activity and safety, the simultaneous expression of multiple genes is frequently required, and short viral-derived 2A sequences are increasingly preferred for this purpose. Concerns exist, however, that these virus-derived sequences may induce unwanted immune responses, and thus diminish persistence of the gene-modified cells after adoptive transfer. Whereas such responses were absent in immunocompromised recipients, potential immunogenicity in immunocompetent individuals remains a concern. We now address whether ex vivo T cell responses can be elicited against the most widely used 2A sequences (2A-Thosea asigna virus (TAV) or 2A-equine rhinitis virus (ERAV), specifically) in immunocompetent individuals. We used a potent ex vivo culture system previously validated to induce T cell responses even against weakly immunogenic antigens. Of the sixteen donors tested, only five released very low levels of interferon-γ in response to 2A-TAV peptide mixtures (single peptide specificity in three donors, adjacent self-antigen peptide specificity in one donor and nonspecific reactivity in one donor). None of them produced cytotoxic activity or responded to 2A-ERAV. These results suggest that exposure to viral-derived 2A sequences is unlikely to produce unwanted T cell responses in immunocompetent individuals and further supports their continued use for studies of human gene 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.