ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Introduction of exogenous T-cell receptors into human hematopoietic progenitors results in exclusion of endogenous T-cell receptor expression.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- Human cDC1 enhance cytotoxic function of CD226+ terminally exhausted tumor-infiltrating lymphocytes.Oncoimmunology · 2025Article
- T Cell Development and Responses in Human Immune System Mice.Annual review of immunology · 2025Review
- Neoantigen-targeted TCR-engineered T cell immunotherapy: current advances and challenges.Biomarker research · 2023Review
- Review
- Robust CAR-T memory formation and function via hematopoietic stem cell delivery.PLoS pathogens · 2021Article
- Gene Families With Stochastic Exclusive Gene Choice Underlie Cell Adhesion in Mammalian Cells.Frontiers in cell and developmental biology · 2021Article
- Reduced positive selection of a human TCR in a swine thymus using a humanized mouse model for xenotolerance induction.Xenotransplantation · 2020Article
- Targeting cancers through TCR-peptide/MHC interactions.Journal of hematology & oncology · 2019Review
- Organoid-Induced Differentiation of Conventional T Cells from Human Pluripotent Stem Cells.Cell stem cell · 2019Article
- IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Humanized Mice Reveal New Insights Into the Thymic Selection of Human Autoreactive CD8Frontiers in immunology · 2019Article
- The Use of the Humanized Mouse Model in Gene Therapy and Immunotherapy for HIV and Cancer.Frontiers in immunology · 2018Review
- Generation of mature T cells from human hematopoietic stem and progenitor cells in artificial thymic organoids.Nature methods · 2017Article
- Genetic Modulation Therapy Through Stem Cell Transplantation for Human Immunodeficiency Virus 1 Infection.Cureus · 2017Review
- Chimeric antigen receptor engineered stem cells: a novel HIV therapy.Immunotherapy · 2017Review
- Engineering HIV-Specific Immunity with Chimeric Antigen Receptors.AIDS patient care and STDs · 2016Article
- Article
- Stem-cell Based Engineered Immunity Against HIV Infection in the Humanized Mouse Model.Journal of visualized experiments : JoVE · 2016Article
- Induction of WT1-specific human CD8+ T cells from human HSCs in HLA class I Tg NOD/SCID/IL2rgKO mice.Blood · 2016Article
- Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID "Meet the Experts" 2015 Workshop Summary.AIDS research and human retroviruses · 2016Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Current tumor immunotherapy approaches include the genetic modification of peripheral T cells to express tumor antigen-specific T-cell receptors (TCRs). The approach, tested in melanoma, has led to some limited success of tumor regression in patients. Yet, the introduction of exogenous TCRs into mature T cells entails an underlying risk; the generation of autoreactive clones due to potential TCR mispairing, and the lack of effective negative selection, as these peripheral cells do not undergo thymic selection following introduction of the exogenous TCR. We have successfully generated MART-1-specific CD8 T cells from genetically modified human hematopoietic stem cells (hHSC) in a humanized mouse model. The advantages of this approach include a long-term source of antigen specific T cells and proper T-cell selection due to thymopoiesis following expression of the TCR. In this report, we examine the molecular processes occurring on endogenous TCR expression and demonstrate that this approach results in exclusive cell surface expression of the newly introduced TCR, and the exclusion of endogenous TCR cell surface expression. This suggests that this stem cell based approach can provide a potentially safer approach for anticancer immunotherapy due to the involvement of thymic selection.
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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.