ArticleThe Journal of biological chemistry2019
Human cytomegalovirus-specific T-cell receptor engineered for high affinity and soluble expression using mammalian cell display.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
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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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Shared inflammatory pathways and therapeutic strategies in COVID-19 and cancer immunotherapy.Journal for immunotherapy of cancer · 2021Pooled it
- Article
- TCR repertoire of human cytotoxic CD4 T cells responding to betaherpesviruses HHV-6B and HCMV.Frontiers in immunology · 2025Article
- Targeting cancer with precision: strategical insights into TCR-engineered T cell therapies.Theranostics · 2025Review
- Strategies and rules for tuning TCR-derived therapy.Expert reviews in molecular medicine · 2023Review
- Nanoparticle-based modulation of CD4Nature communications · 2022Article
- Article
- Engineering the T cell receptor for fun and profit: Uncovering complex biology, interrogating the immune system, and targeting disease.Current opinion in structural biology · 2022Review
- Mammalian Display Platform for the Maturation of Bispecific TCR-Based Molecules.Antibodies (Basel, Switzerland) · 2022Article
- An antibody Fc engineered for conditional antibody-dependent cellular cytotoxicity at the low tumor microenvironment pH.The Journal of biological chemistry · 2022Article
- Rapid characterization of spike variants via mammalian cell surface display.Molecular cell · 2021Article
- Engineering soluble T-cell receptors for therapy.The FEBS journal · 2021Review
- Immunotherapy with adoptive cytomegalovirus-specific T cells transfer: Summarizing latest gene engineering techniques.Health science reports · 2021Review
- Affinity Maturation of a T-Cell Receptor-Like Antibody Specific for a Cytomegalovirus pp65-Derived Peptide Presented by HLA-A*02:01.International journal of molecular sciences · 2021Article
- Competition-Based Cell Assay Employing Soluble T Cell Receptors to Assess MHC Class II Antigen Processing and Presentation.The AAPS journal · 2021Article
- Review
- Weaponizing T-cell receptors through molecular engineering.The Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
T-cell receptors (TCR) have considerable potential as therapeutics and antibody-like reagents to monitor disease progression and vaccine efficacy. Whereas antibodies recognize only secreted and surface-bound proteins, TCRs recognize otherwise inaccessible disease-associated intracellular proteins when they are presented as processed peptides bound to major histocompatibility complexes (pMHC). TCRs have been primarily explored for cancer therapy applications but could also target infectious diseases such as cytomegalovirus (CMV). However, TCRs are more difficult to express and engineer than antibodies, and advanced methods are needed to enable their widespread use. Here, we engineered the human CMV-specific TCR RA14 for high-affinity and robust soluble expression. To achieve this, we adapted our previously reported mammalian display system to present TCR extracellular domains and used this to screen CDR3 libraries for clones with increased pMHC affinity. After three rounds of selection, characterized clones retained peptide specificity and activation when expressed on the surface of human Jurkat T cells. We obtained high yields of soluble, monomeric protein by fusing the TCR extracellular domains to antibody hinge and Fc constant regions, adding a stabilizing disulfide bond between the constant domains and disrupting predicted glycosylation sites. One variant exhibited 50 nm affinity for its cognate pMHC, as measured by surface plasmon resonance, and specifically stained cells presenting this pMHC. Our work has identified a human TCR with high affinity for the immunodominant CMV peptide and offers a new strategy to rapidly engineer soluble TCRs for biomedical applications.
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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.