ArticleBlood2013
Enhanced-affinity murine T-cell receptors for tumor/self-antigens can be safe in gene therapy despite surpassing the threshold for thymic selection.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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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.
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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
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- The Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review.Technology in cancer research & treatment · 2019Pooled it
- Advances inMolecular therapy. Nucleic acids · 2026Review
- Generation and evaluation of cancer binding capacity of HLA-A2-WT1 complex-targeting antibody.Immunology letters · 2024Article
- Engineering second-generation TCR-T cells by site-specific integration of TRAF-binding motifs into theJournal for immunotherapy of cancer · 2023Article
- How I treat high-risk acute myeloid leukemia using preemptive adoptive cellular immunotherapy.Blood · 2023Article
- WT1-specific TCRs directed against newly identified peptides install antitumor reactivity against acute myeloid leukemia and ovarian carcinoma.Journal for immunotherapy of cancer · 2022Article
- Review
- Development of Cancer Immunotherapies.Cancer treatment and research · 2022Article
- In vitro-transcribed antigen receptor mRNA nanocarriers for transient expression in circulating T cells in vivo.Nature communications · 2020Article
- Review
- Review
- T Cell Receptor Engineered Lymphocytes for Cancer Therapy.Current protocols in immunology · 2020Article
- Review
- Potentiating the Antitumor Activity of Cytotoxic T CellsFrontiers in immunology · 2020Article
- Immunological and Clinical Impact of Manipulated and Unmanipulated DLI after Allogeneic Stem Cell Transplantation of AML Patients.Journal of clinical medicine · 2019Review
- Preclinical development of T-cell receptor-engineered T-cell therapy targeting the 5T4 tumor antigen on renal cell carcinoma.Cancer immunology, immunotherapy : CII · 2019Article
- Developing neoantigen-targeted T cell-based treatments for solid tumors.Nature medicine · 2019Review
- Improving T Cell Receptor On-Target Specificity via Structure-Guided Design.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Type I IFN blockade uncouples immunotherapy-induced antitumor immunity and autoimmune toxicity.The Journal of clinical investigation · 2019Article
- The intersection of affinity and specificity in the development and optimization of T cell receptor based therapeutics.Seminars in cell & developmental biology · 2018Review
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
Many of the most promising tumor antigens for T-cell-based cancer immunotherapies are unmodified self-antigens. Unfortunately, the avidity of T cells specific for these antigens is limited by central tolerance during T-cell development in the thymus, resulting in decreased anti-tumor efficacy of these T cells. One approach to overcoming this obstacle is to mutate T-cell receptor (TCR) genes from naturally occurring T cells to enhance the affinity for the target antigen. These enhanced-affinity TCRs can then be developed for use in TCR gene therapy. Although TCRs with significantly enhanced affinity have been generated using this approach, it is not clear whether these TCRs, which bypass the affinity limits imposed by negative selection, remain unresponsive to the low levels of self-antigen generally expressed by some normal tissues. Here we show that 2 variants of a high-affinity WT1-specific TCR with enhanced affinity for WT1 are safe and do not mediate autoimmune tissue infiltration or damage when transduced into peripheral CD8 T cells and transferred in vivo. However, if expressed in developing T cells and subjected to thymic selection, the same enhanced-affinity TCRs signal tolerance mechanisms in the thymus, resulting in T cells with attenuated antigen sensitivity in the periphery.
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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.