ArticleCancer immunology research2015
Optimization of T-cell Reactivity by Exploiting TCR Chain Centricity for the Purpose of Safe and Effective Antitumor TCR Gene Therapy.
Article in Cancer immunology research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- One-step generation of T-cell receptor knock-in mice in the TCRβ locus.The EMBO journal · 2026Article
- Tumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patient.Nature communications · 2024Article
- Mini-TCRs: Truncated T cell receptors to generate T cells from induced pluripotent stem cells.Molecular therapy. Methods & clinical development · 2023Article
- T Cell Receptor Chain Centricity: The Phenomenon and Potential Applications in Cancer Immunotherapy.International journal of molecular sciences · 2023Review
- Establishment of a novel NFAT-GFP reporter platform useful for the functional avidity maturation of HLA class II-restricted TCRs.Cancer immunology, immunotherapy : CII · 2023Article
- Physiological and Functional Effects of Dominant Active TCRα Expression in Transgenic Mice.International journal of molecular sciences · 2023Article
- Targeting the melanoma-associated antigen CSPG4 with HLA-C*07:01-restricted T-cell receptors.Frontiers in immunology · 2023Article
- Unique features of the TCR repertoire of reactivated memory T cells in the experimental mouse tumor model.Computational and structural biotechnology journal · 2023Article
- Affinity-matured HLA class II dimers for robust staining of antigen-specific CD4Nature biotechnology · 2021Article
- Proteogenomic identification of an immunogenic HLA class I neoantigen in mismatch repair-deficient colorectal cancer tissue.JCI insight · 2021Article
- A single-chain antibody generation system yielding CAR-T cells with superior antitumor function.Communications biology · 2021Article
- Adoptive Immunotherapy Based on Chain-Centric TCRs in Treatment of Infectious Diseases.iScience · 2020Article
- Article
- High Frequency Production of T Cell-Derived iPSC Clones Capable of Generating Potent Cytotoxic T Cells.Molecular therapy. Methods & clinical development · 2020Article
- Direct comparison of target-reactivity and cross-reactivity induced by CAR- and BiTE-redirected T cells for the development of antibody-based T-cell therapy.Scientific reports · 2019Article
- Dominant role of the α-chain in rejection of tumor cells bearing a specific alloantigen in TCRα transgenic mice and inOncotarget · 2019Article
- Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers.Nature medicine · 2019Article
- A Subset of Human Autoreactive CD1c-Restricted T Cells Preferentially Expresses TRBV4-1Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Key Residues at Third CDR3β Position Impact Structure and Antigen Recognition of Human Invariant NK TCRs.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Generating De Novo Antigen-specific Human T Cell Receptors by Retroviral Transduction of Centric Hemichain.Journal of visualized experiments : JoVE · 2016Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Adoptive transfer of T cells redirected by a high-affinity antitumor T-cell receptor (TCR) is a promising treatment modality for cancer patients. Safety and efficacy depend on the selection of a TCR that induces minimal toxicity and elicits sufficient antitumor reactivity. Many, if not all, TCRs possess cross-reactivity to unrelated MHC molecules in addition to reactivity to target self-MHC/peptide complexes. Some TCRs display chain centricity, in which recognition of MHC/peptide complexes is dominated by one of the TCR hemi-chains. In this study, we comprehensively studied how TCR chain centricity affects reactivity to target self-MHC/peptide complexes and alloreactivity using the TCR, clone TAK1, which is specific for human leukocyte antigen-A*24:02/Wilms tumor 1(235-243) (A24/WT1(235)) and cross-reactive with B*57:01 (B57). The TAK1β, but not the TAK1α, hemi-chain possessed chain centricity. When paired with multiple clonotypic TCRα counter-chains encoding TRAV12-2, 20, 36, or 38-2, the de novo TAK1β-containing TCRs showed enhanced, weakened, or absent reactivity to A24/WT1(235) and/or to B57. T cells reconstituted with these TCRα genes along with TAK1β possessed a very broad range (>3 log orders) of functional and structural avidities. These results suggest that TCR chain centricity can be exploited to enhance desired antitumor TCR reactivity and eliminate unwanted TCR cross-reactivity. TCR reactivity to target MHC/peptide complexes and cross-reactivity to unrelated MHC molecules are not inextricably linked and are separable at the TCR sequence level. However, it is still mandatory to carefully monitor for possible harmful toxicities caused by adoptive transfer of T cells redirected by thymically unselected TCRs.
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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.