ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Stable, Nonviral Expression of Mutated Tumor Neoantigen-specific T-cell Receptors Using the Sleeping Beauty Transposon/Transposase System.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- The Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review.Technology in cancer research & treatment · 2019Pooled it
- Neoantigen screening identifies broad TP53 mutant immunogenicity in patients with epithelial cancers.The Journal of clinical investigation · 2019Trial
- TCR-Based Antigen-Specific Therapy for Type 1 Diabetes Mellitus: From Editing Autoreactive Clones to Tolerance Induction.International journal of molecular sciences · 2025Review
- Current developments in T-cell receptor therapy for acute myeloid leukemia.Blood advances · 2025Review
- Targeted gene delivery systems for T-cell engineering.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Novel insights into TCR-T cell therapy in solid neoplasms: optimizing adoptive immunotherapy.Experimental hematology & oncology · 2024Review
- Neoantigen-targeted TCR-engineered T cell immunotherapy: current advances and challenges.Biomarker research · 2023Review
- Challenges and new technologies in adoptive cell therapy.Journal of hematology & oncology · 2023Review
- Racing CARs to veterinary immuno-oncology.Frontiers in veterinary science · 2023Review
- Review
- Adoptive T-cell Immunotherapy: Perfecting Self-Defenses.Experientia supplementum (2012) · 2022Article
- Cancer Therapy With TCR-Engineered T Cells: Current Strategies, Challenges, and Prospects.Frontiers in immunology · 2022Review
- Choosing the Right Tool for Genetic Engineering: Clinical Lessons from Chimeric Antigen Receptor-T Cells.Human gene therapy · 2021Review
- Evolution of CD8Cells · 2021Review
- CAR-T and other adoptive cell therapies for B cell malignancies.Journal of the National Cancer Center · 2021Review
- Contemporary Transposon Tools: A Review and Guide through Mechanisms and Applications ofInternational journal of molecular sciences · 2021Review
- Engineered T Cell Therapy for Gynecologic Malignancies: Challenges and Opportunities.Frontiers in immunology · 2021Review
- Arming HSV-Based Oncolytic Viruses with the Ability to Redirect the Host's Innate Antiviral Immunity to Attack Tumor Cells.Molecular therapy oncolytics · 2020Article
- Review
- CD4 Inhibits Helper T Cell Activation at Lower Affinity Threshold for Full-Length T Cell Receptors Than Single Chain Signaling Constructs.Frontiers in immunology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Neoantigens unique to each patient's tumor can be recognized by autologous T cells through their T-cell receptor (TCR) but the low frequency and/or terminal differentiation of mutation-specific T cells in tumors can limit their utility as adoptive T-cell therapies. Transfer of TCR genes into younger T cells from peripheral blood with a high proliferative potential could obviate this problem. We generated a rapid, cost-effective strategy to genetically engineer cancer patient T cells with TCRs using the clinical Sleeping Beauty transposon/transposase system. Patient-specific TCRs reactive against HLA-A*0201-restriced neoantigens AHNAK(S2580F) or ERBB2(H473Y) or the HLA-DQB*0601-restricted neoantigen ERBB2IP(E805G) were assembled with murine constant chains and cloned into Sleeping Beauty transposons. Patient peripheral blood lymphocytes were coelectroporated with SB11 transposase and Sleeping Beauty transposon, and transposed T cells were enriched by sorting on murine TCRβ (mTCRβ) expression. Rapid expansion of mTCRβ(+) T cells with irradiated allogeneic peripheral blood lymphocytes feeders, OKT3, interleukin-2 (IL-2), IL-15, and IL-21 resulted in a preponderance of effector (CD27(-)CD45RA(-)) and less-differentiated (CD27(+)CD45RA(+)) T cells. Transposed T cells specifically mounted a polyfunctional response against cognate mutated neoantigens and tumor cell lines. Thus, Sleeping Beauty transposition of mutation-specific TCRs can facilitate the use of personalized T-cell therapy targeting unique neoantigens.
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What OpenQuestion holds
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.