Targeting Jurkat T Lymphocyte Leukemia Cells by an Engineered Interferon-Alpha Hybrid Molecule

Yu, Dehai; Du, Zhonghua; Li, Wei; Chen, Huaqiu; Ye, Songgen; Hoffman, Andrew R.; Cui, Jiuwei; Hu, Ji-Fan

doi:10.1159/000477601

Cited by 7 publications

(5 citation statements)

References 38 publications

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“…Total cell protein was extracted with radioimmunoprecipitation assay (RIPA) buffer supplemented with cocktail protease inhibitor (Roche), and the protein concentration was determined by a Pierce BCA protein assay kit as previously described. 59 Twenty micrograms of total cell protein were separated on 12% SDS-PAGE and electrophoretically transferred to polyvinylidene fluoride (PVDF) membranes (0.45 μm, Millipore, Billerica, MA, USA). After blocking with 5% skim milk, the membranes were incubated with monoclonal antibodies against IGF1R (Santa Cruz Biotechnology, CA) and were detected with the enhanced chemiluminescence system (ECL, Thermo).…”

Section: Methodsmentioning

confidence: 99%

Targeting the IGF1R Pathway in Breast Cancer Using Antisense lncRNA-Mediated Promoter cis Competition

Pian

Xue

Kang

et al. 2018

Molecular Therapy - Nucleic Acids

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Aberrant insulin-like growth factor I receptor (IGF1R) signaling pathway serves as a well-established target for cancer drug therapy. The intragenic antisense long noncoding RNA (lncRNA) IRAIN, a putative tumor suppressor, is downregulated in breast cancer cells, while IGF1R is overexpressed, leading to an abnormal IGF1R/IRAIN ratio that promotes tumor growth. To precisely target this pathway, we developed an “antisense lncRNA-mediated intragenic cis competition” (ALIC) approach to therapeutically correct the elevated IGF1R/IRAIN bias in breast cancer cells. We used CRISPR-Cas9 gene editing to target the weak promoter of IRAIN antisense lncRNA and showed that in targeted clones, intragenic activation of the antisense lncRNA potently competed in cis with the promoter of the IGF1R sense mRNA. Notably, the normalization of IGF1R/IRAIN transcription inhibited the IGF1R signaling pathway in breast cancer cells, decreasing cell proliferation, tumor sphere formation, migration, and invasion. Using “nuclear RNA reverse transcription-associated trap” sequencing, we uncovered an IRAIN lncRNA-specific interactome containing gene targets involved in cell metastasis, signaling pathways, and cell immortalization. These data suggest that aberrantly upregulated IGF1R in breast cancer cells can be precisely targeted by cis transcription competition, thus providing a useful strategy to target disease genes in the development of novel precision medicine therapies.

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Section: Methodsmentioning

confidence: 99%

Targeting the IGF1R Pathway in Breast Cancer Using Antisense lncRNA-Mediated Promoter cis Competition

Pian

Xue

Kang

et al. 2018

Molecular Therapy - Nucleic Acids

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“…Searching the MimoDatabase that contains all peptides derived from PD indicated matches for S1–S3 of the third-round Sanger pool (Figure B) and for several highly abundant NGS sequences (Table S3). These sequences were previously selected against biotargets , that differ from PP. There are two evolutionary advantages in the selection process that drive phage enrichment: (i) strong binding to the target and (ii) superior amplification rates in Escherichia coli hosts .…”

mentioning

confidence: 99%

Combining Phage Display and Next-Generation Sequencing for Materials Sciences: A Case Study on Probing Polypropylene Surfaces

Juds

Schmidt²,

Weller

et al. 2020

J. Am. Chem. Soc.

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Phage display biopanning with Illumina next-generation sequencing (NGS) is applied to reveal insights into peptide-based adhesion domains for polypropylene (PP). One biopanning round followed by NGS selects robust PP-binding peptides that are not evident by Sanger sequencing. NGS provides a significant statistical base that enables motif analysis, statistics on positional residue depletion/enrichment, and data analysis to suppress false-positive sequences from amplification bias. The selected sequences are employed as water-based primers for PP–metal adhesion to condition PP surfaces and increase adhesive strength by 100% relative to nonprimed PP.

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“…The MT2 cell line is an adult T cell leukemia (ATL) cell line with aberrant CD4 expression established by co-culture of normal human cord leukocytes with leukemic cells from ATL patients [18]. Jurkat cells are immortalized T lymphocytes obtained from a patient with T cell leukemia [19]. CD4 expression on MT2 and Jurkat cells was counterchecked by flow cytometry prior to experiments.…”

Section: Resultsmentioning

confidence: 99%

AAV-MediatedIn VivoCAR Gene Therapy for Targeting Human T Cell Leukemia

Nawaz

Huang

et al. 2021

Preprint

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Chimeric antigen receptor (CAR) T cell therapy is the most active field in immuno-oncology and brings substantial benefit to patients with B cell malignancies. However, the complex procedure for CAR T cell generation hampers its widespread applications. Here, we describe a novel approach in which human CAR T cells can be generated within the host upon injecting an Adeno-associated virus （AAV）vector carrying the CAR gene, which we call AAV delivering CAR gene therapy (ACG). Upon single infusion into a humanized NCG tumor mouse model of human T cell leukemia, AAV generates sufficient numbers of potent in vivo CAR cells, resulting in tumor regression; these in vivo generated CAR cells produce antitumor immunological characteristics. This instantaneous generation of in vivo CAR T cells may bypass the need for patient lymphodepletion, as well as the ex vivo processes of traditional CAR T cell production, which may make CAR therapy simpler and less expensive. It may allow the development of intricate, individualized treatments in the form of on-demand and diverse therapies.

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Targeting Jurkat T Lymphocyte Leukemia Cells by an Engineered Interferon-Alpha Hybrid Molecule

Cited by 7 publications

References 38 publications

Targeting the IGF1R Pathway in Breast Cancer Using Antisense lncRNA-Mediated Promoter cis Competition

Targeting the IGF1R Pathway in Breast Cancer Using Antisense lncRNA-Mediated Promoter cis Competition

Combining Phage Display and Next-Generation Sequencing for Materials Sciences: A Case Study on Probing Polypropylene Surfaces

AAV-MediatedIn VivoCAR Gene Therapy for Targeting Human T Cell Leukemia

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