ArticleHuman gene therapy2013
Enhanced function of redirected human T cells expressing linker for activation of T cells that is resistant to ubiquitylation.
Article in Human gene therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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
13 citing papers in PubMed, 20 citations in OpenAlex.
- Advances inMolecular therapy. Nucleic acids · 2026Review
- Roles of ubiquitination in the crosstalk between tumors and the tumor microenvironment (Review).International journal of oncology · 2022Review
- Regulating the discriminatory response to antigen by T-cell receptor.Bioscience reports · 2022Review
- RNA-electroporated T cells for cancer immunotherapy.Oncoimmunology · 2020Review
- Bypassing ubiquitination enables LAT recycling to the cell surface and enhanced signaling in T cells.PloS one · 2020Article
- Microclusters as T Cell Signaling Hubs: Structure, Kinetics, and Regulation.Frontiers in cell and developmental biology · 2020Review
- Activated iNKT cells enhance the anti-tumor effect of antigen specific CD8 T cells on mesothelin-expressing salivary gland cancer.BMC cancer · 2018Article
- Intracellular Delivery by Membrane Disruption: Mechanisms, Strategies, and Concepts.Chemical reviews · 2018Review
- Effect ofExperimental and therapeutic medicine · 2016Article
- Enhanced T-cell activation and differentiation in lymphocytes from transgenic mice expressing ubiquitination-resistant 2KR LAT molecules.Gene therapy · 2015Article
- Gene-engineered T cells for cancer therapy.Nature reviews. Cancer · 2013Review
- Trial Watch: Adoptive cell transfer for anticancer immunotherapy.Oncoimmunology · 2013Article
- Immunotherapy of malignant disease using chimeric antigen receptor engrafted T cells.ISRN oncology · 2012Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
It is likely that the enhancement of signaling after antigenic stimulation, particularly in the tumor microenvironment, would improve the function of adoptively transferred T cells. Linker for activation of T cells (LAT) plays a central role in T cell activation. We hypothesized that the ubiquitylation-resistant form of LAT in cells would enhance T cell signaling and thus augment antitumor activity. To test this, human CD4(+) or CD8(+) T cells were electroporated with small interfering RNA (siRNA) to repress endogenous LAT and ubiquitylation-resistant LAT 2KR or wild-type LAT mRNA was introduced for reexpression. Significantly enhanced phosphorylation of LAT and phospholipase C-γ (PLCγ) was observed, and augmented calcium signaling after T cell receptor (TCR) triggering was observed in LAT 2KR-expressing T cells. TCR-induced calcium signaling was abrogated in LAT knockdown cells, but the baseline was higher than that of control siRNA-electroporated cells, suggesting a fundamental requirement of LAT to maintain calcium homeostasis. Redirected LAT 2KR T cells expressing a chimeric antigen receptor or an MHC class I-restricted TCR showed augmented function as assessed by enhanced cytokine secretion and cytotoxicity. These results indicate that interruption of LAT ubiquitylation is a promising strategy to augment effector T cell function for adoptive cell therapy.
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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.