ArticleImmunologic research2006
Redirection of T cells by delivering a transgenic mouse-derived MDM2 tumor antigen-specific TCR and its humanized derivative is governed by the CD8 coreceptor and affects natural human TCR expression.
Article in Immunologic research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 49 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
- Modifications to rhesus macaque TCR constant regions improve TCR cell surface expression.PloS one · 2025Article
- Modifications outside CDR1, 2 and 3 of the TCR variable β domain increase TCR expression and antigen-specific function.Frontiers in immunology · 2023Article
- Review
- Characterization and modulation of anti-αβTCR antibodies and their respective binding sites at the βTCR chain to enrich engineered T cells.Molecular therapy. Methods & clinical development · 2021Article
- Review
- T cell receptor-engineered T cells for leukemia immunotherapy.Cancer cell international · 2019Review
- IL-10 inducible CD8Cancer immunology, immunotherapy : CII · 2018Article
- RNAi-mediated TCR knockdown prevents autoimmunity in mice caused by mixed TCR dimers following TCR gene transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Adoptive immunotherapy for cancer or viruses.Annual review of immunology · 2014Review
- Isolation of human MHC class II-restricted T cell receptors from the autologous T-cell repertoire with potent anti-leukaemic reactivity.Immunology · 2012Article
- How (specific) would like your T-cells today? Generating T-cell therapeutic function through TCR-gene transfer.Frontiers in immunology · 2012Article
- TCR mispairing in genetically modified T cells was detected by fluorescence resonance energy transfer.Molecular biology reports · 2010Article
- Targeting the epidermal growth factor receptor (HER) family by T cell receptor gene-modified T lymphocytes.Journal of molecular medicine (Berlin, Germany) · 2010Article
- Rebalancing immune specificity and function in cancer by T-cell receptor gene therapy.Archivum immunologiae et therapiae experimentalis · 2010Review
- NCI First International Workshop on The Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Cell Transplantation: report from the committee on prevention of relapse following allogeneic cell transplantation for hematologic malignancies.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2010Review
- Mixed T cell receptor dimers harbor potentially harmful neoreactivity.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- TCR transgenes and transgene cassettes for TCR gene therapy: status in 2008.Cancer immunology, immunotherapy : CII · 2009Review
- Increasing functional avidity of TCR-redirected T cells by removing defined N-glycosylation sites in the TCR constant domain.The Journal of experimental medicine · 2009Article
- Enhanced functionality of T cell receptor-redirected T cells is defined by the transgene cassette.Journal of molecular medicine (Berlin, Germany) · 2008Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retroviral transfer of T cell antigen receptor (TCR) genes selected by circumventing tolerance to broad tumor- and leukemia-associated antigens in human leukocyte antigen (HLA)-A*0201 (A2.1) transgenic (Tg) mice allows the therapeutic reprogramming of human T lymphocytes. Using a human CD8 x A2.1/Kb mouse derived TCR specific for natural peptide-A2.1 (pA2.1) complexes comprising residues 81-88 of the human homolog of the murine double-minute 2 oncoprotein, MDM2(81-88), we found that the heterodimeric CD8 alpha beta coreceptor, but not normally expressed homodimeric CD8 alpha alpha, is required for tetramer binding and functional redirection of TCR- transduced human T cells. CD8+T cells that received a humanized derivative of the MDM2 TCR bound pA2.1 tetramers only in the presence of an anti-human-CD8 anti-body and required more peptide than wild-type (WT) MDM2 TCR+T cells to mount equivalent cytotoxicity. They were, however, sufficiently effective in recognizing malignant targets including fresh leukemia cells. Most efficient expression of transduced TCR in human T lymphocytes was governed by mouse as compared to human constant (C) alphabeta domains, as demonstrated with partially humanized and murinized TCR of primary mouse and human origin, respectively. We further observed a reciprocal relationship between the level of Tg WT mouse relative to natural human TCR expression, resulting in T cells with decreased normal human cell surface TCR. In contrast, natural human TCR display remained unaffected after delivery of the humanized MDM2 TCR. These results provide important insights into the molecular basis of TCR gene therapy of malignant disease.
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