ArticleJournal of leukocyte biology2018
TCR modifications that enhance chain pairing in gene-modified T cells can augment cross-reactivity and alleviate CD8 dependence.
Article in Journal of leukocyte biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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Who cites it
13 citing papers in PubMed, 10 citations in OpenAlex.
- Simultaneous gene engineering of T cells with multiple neoantigen-specific T cell receptors for adoptive cell transfer.Molecular therapy. Advances · 2026Article
- Engineering a Second Interchain Disulfide Bond in the αβ T-Cell Receptor Constant Domain: A Powerful Strategy to Enhance Stability, Pairing Fidelity, and Therapeutic Efficacy in TCR-T Cell Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Targeting solid tumors with TCR-T cells: mechanisms, progress, and challenges.Frontiers in oncology · 2026Review
- Non-canonical and induced neoantigens as emerging sources of cancer-specific immunotherapy targets.Frontiers in immunology · 2026Review
- Adoptive T Cell Therapy Targeting MAGE-A4.Cancers · 2025Review
- 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
- Review
- Adoptive T-cell Immunotherapy: Perfecting Self-Defenses.Experientia supplementum (2012) · 2022Article
- Review
- Understanding TCR affinity, antigen specificity, and cross-reactivity to improve TCR gene-modified T cells for cancer immunotherapy.Cancer immunology, immunotherapy : CII · 2019Review
- 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
- Tuning T-Cell Receptor Affinity to Optimize Clinical Risk-Benefit When Targeting Alpha-Fetoprotein-Positive Liver Cancer.Hepatology (Baltimore, Md.) · 2019Article
- Safety and Tolerability of Adoptive Cell Therapy in Cancer.Drug safety · 2019Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
T cell receptor (TCR) gene-modified T cells are a promising immunotherapy but require refinement to improve clinical responses and limit off-target toxicities. A variety of TCR and gene-delivery vector modifications have been developed to enhance introduced TCR expression and limit introduced/endogenous TCR chain mispairing, improving target antigen recognition and minimizing mispairing-induced cross-reactivity. Using our well-characterized HCV1406 TCR, we previously compared the impact of various chain pairing enhancing modifications on TCR expression and cognate antigen recognition. HCV1406 TCR is also natively cross-reactive against naturally occurring altered peptide ligands (APLs), which was shown to be dependent on high TCR surface density. In this report, we observed in a Jurkat model that absent TCR chain pairing competition alleviated CD8-dependent APL recognition and induced novel cross-reactivity of HCV1406 TCR. We then compared chain pairing enhancing modifications' effects on TCR cross-reactivity in Jurkat and T cells, showing C-terminal leucine zippers and constant region murinization alleviated CD8 dependence and induced novel APL recognition. While modifications enhancing TCR chain pairing intend to avoid cross-reactivity by limiting mispairing with the endogenous TCR, these data suggest they may also enhance natural cross-reactivity and reduce dependence on CD8. These observations have significant implications on the design/implementation of TCR gene-modified T cells.
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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.