ArticleNature communications2020
Computational stabilization of T cell receptors allows pairing with antibodies to form bispecifics.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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
23 citing papers in PubMed, 37 citations in OpenAlex.
- Computational design of optimized and preferentially paired human TCR constant regions for improved T cell function.Science advances · 2026Article
- Therapeutic peptides and proteins: Status and developments in drug delivery.Journal of controlled release : official journal of the Controlled Release Society · 2026Review
- Targeted therapies in pediatric oncology: A start.Molecular therapy. Oncology · 2026Review
- Shared PRAME epitopes are T-cell targets in NUT carcinoma.Journal for immunotherapy of cancer · 2026Article
- Computational design of orthogonal TCR α/β interfaces for dual-TCR therapeutics.bioRxiv : the preprint server for biology · 2026Article
- Sideways lipid presentation by the antigen-presenting molecule CD1c.Nature communications · 2025Article
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- Large protein-like leader peptides engage differently with RiPP halogenases and lanthionine synthetases.Nature communications · 2025Article
- A conserved human CD4+ T cell subset recognizing the mycobacterial adjuvant trehalose monomycolate.The Journal of clinical investigation · 2024Article
- Investigating the role of non-synonymous variant D67N of ADGRE2 in chronic myeloid leukemia.BMC cancer · 2024Article
- Article
- BiSpec Pairwise AI: guiding the selection of bispecific antibody target combinations with pairwise learning and GPT augmentation.Journal of cancer research and clinical oncology · 2024Article
- T Cell Receptor-Directed Bispecific T Cell Engager Targeting MHC-Linked NY-ESO-1 for Tumor Immunotherapy.Biomedicines · 2024Article
- Stabilizing proteins, simplified: A Rosetta-based webtool for predicting favorable mutations.Protein science : a publication of the Protein Society · 2022Article
- A novel IgG Fc by computer-aided design enhances heavy-chain heterodimerization in bi- or trispecific antibodies.Antibody therapeutics · 2022Article
- 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
- Generalizable design parameters for soluble T cell receptor-based T cell engagers.Journal for immunotherapy of cancer · 2022Article
- Emerging new therapeutic antibody derivatives for cancer treatment.Signal transduction and targeted therapy · 2022Review
- Engineering soluble T-cell receptors for therapy.The FEBS journal · 2021Review
- Designed, highly expressing, thermostable dengue virus 2 envelope protein dimers elicit quaternary epitope antibodies.Science advances · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Recombinant T cell receptors (TCRs) can be used to redirect naïve T cells to eliminate virally infected or cancerous cells; however, they are plagued by low stability and uneven expression. Here, we use molecular modeling to identify mutations in the TCR constant domains (Cα/Cβ) that increase the unfolding temperature of Cα/Cβ by 20 °C, improve the expression of four separate α/β TCRs by 3- to 10-fold, and improve the assembly and stability of TCRs with poor intrinsic stability. The stabilizing mutations rescue the expression of TCRs destabilized through variable domain mutation. The improved stability and folding of the TCRs reduces glycosylation, perhaps through conformational stabilization that restricts access to N-linked glycosylation enzymes. The Cα/Cβ mutations enables antibody-like expression and assembly of well-behaved bispecific molecules that combine an anti-CD3 antibody with the stabilized TCR. These TCR/CD3 bispecifics can redirect T cells to kill tumor cells with target HLA/peptide on their surfaces in vitro.
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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.