Expression of a dominant T-cell receptor can reduce toxicity and enhance tumor protection of allogeneic T-cell therapy

Holler, Angelika; Zech, Mathias; Ghorashian, Sara; Pike, Rebecca; Hotblack, Alastair; Veliça, Pedro; Xue, Shao-An; Chakraverty, Ronjon; Morris, Emma; Stauss, Hans J.

doi:10.3324/haematol.2015.132712

Cited by 2 publications

(3 citation statements)

References 33 publications

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“…32 In addition, a large number of studies have shown that the T cell signaling pathway is closely related to cancer. 20,33,34 Among these target genes, survival analysis, and the Oncomine database confirmed that these target genes were negatively correlated with GC. SMARCA2 is reportedly downregulated in GC.…”

Section: Discussionmentioning

confidence: 87%

“…Type 1 diabetes significantly increased the risk of GC in the subgroup meta‐analysis by type of cancer . In addition, a large number of studies have shown that the T cell signaling pathway is closely related to cancer . Among these target genes, survival analysis, and the Oncomine database confirmed that these target genes were negatively correlated with GC.…”

Section: Discussionmentioning

confidence: 91%

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Serum miR‐515‐3p, a potential new RNA biomarker, is involved in gastric carcinoma

Han

Zhao

et al. 2019

J of Cellular Biochemistry

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Objectives microRNAs (miRNAs) have provided a new opportunity for developing diagnostic biomarkers and effective therapeutic targets in gastric cancer (GC). In this study, we aimed to investigate the relationship between miR‐515‐3p and GC development. Experimental Design The Gene Expression Omnibus (GEO) database was used for screening genes and miRNA and for 2R analysis. miRNA prediction target genes and screening key genes were analyzed using protein interactions (PPI) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A network of miRNA‐mRNA interactions was predicated by Cytoscape (v.3.5.1), Institute of Systems Biology & University of California, San Diego & Pasteur institute & University of California, San Francisco. Finally, miR‐515‐3p levels were detected by quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) in gastric cells and plasma levels. Then, the association between the expression level of miR‐515‐3p and the clinicopathological features of patients with GC was further analyzed. Observations and Conclusions We found that miR‐515‐3p was markedly overexpressed in individuals with GC compared with that in normal gastric cells (NCs) and the surgery group (P < 0.0001). In addition, receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) value of 0.8555 for miR‐515‐3p. Significance Our results present new information to the field of gastric cancer and has done a good job of creating an initial hypothesis using the database as well as validate their initial results. These results suggest that serum miR‐515‐3p is a novel potential biomarker for the detection of GC.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 91%

Serum miR‐515‐3p, a potential new RNA biomarker, is involved in gastric carcinoma

Han

Zhao

et al. 2019

J of Cellular Biochemistry

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“…The engineering of T cells with genes encoding TCR chains, or chimeric antigen receptors (CARs) is an efficient strategy to produce cells for antigen-specific T cell therapy in the clinical setting (1). TCR gene therapy typically relies on transferring antigen-specific T cell receptor alpha and beta chains into the autologous T cells obtained from patients (2). Several promising clinical benefits have been obtained using TCR gene therapy to target tumour associated antigens, cancer testis antigens and viral antigens (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Modifications outside CDR1, 2 and 3 of the TCR variable β domain increase TCR expression and antigen-specific function

et al. 2023

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T cell receptor (TCR) gene modified T cells are a promising form of adoptive cellular therapy 30 against human malignancies and viral infections. Since the first human clinical trial was carried 31 out in 2006, several strategies have been developed to improve the efficacy and safety of TCR 32 engineered T cells by enhancing the surface expression of the introduced therapeutic TCRs 33 whilst reducing the mis-pairing with endogenous TCR chains. In this study, we explored how 34 modifications of framework residues in the TCR variable domains affect TCR expression and 35 function. We used bioinformatic and protein structural analyses to identify candidate amino 36 acid residues in the framework of the variable β domain predicted to drive high TCR surface 37 expression. Changes of these residues in poorly expressed TCRs resulted in improved surface 38 expression and boosted target cell specific killing by engineered T cells expressing the 39 modified TCRs. Overall, these results indicate that small changes in the framework of the TCR 40 variable domains can result in improved expression and functionality, while at the same time 41 reducing the risk of toxicity associated with TCR mis-pairing.

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Expression of a dominant T-cell receptor can reduce toxicity and enhance tumor protection of allogeneic T-cell therapy

Cited by 2 publications

References 33 publications

Serum miR‐515‐3p, a potential new RNA biomarker, is involved in gastric carcinoma

Serum miR‐515‐3p, a potential new RNA biomarker, is involved in gastric carcinoma

Modifications outside CDR1, 2 and 3 of the TCR variable β domain increase TCR expression and antigen-specific function

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