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| 2. |
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| 3. |
- Pasetto, A, et al.
(författare)
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Generation of T-cell receptors targeting a genetically stable and immunodominant cytotoxic T-lymphocyte epitope within hepatitis C virus non-structural protein 3
- 2012
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Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 93:Pt 2, s. 247-258
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis C virus (HCV) is a major cause of severe liver disease, and one major contributing factor is thought to involve a dysfunction of virus-specific T-cells. T-cell receptor (TCR) gene therapy with HCV-specific TCRs would increase the number of effector T-cells to promote virus clearance. We therefore took advantage of HLA-A2 transgenic mice to generate multiple TCR candidates against HCV using DNA vaccination followed by generation of stable T-cell–BW (T-BW) tumour hybrid cells. Using this approach, large numbers of non-structural protein 3 (NS3)-specific functional T-BW hybrids can be generated efficiently. These predominantly target the genetically stable HCV genotype 1 NS31073–1081 CTL epitope, frequently associated with clearance of HCV in humans. These T-BW hybrid clones recognized the NS31073 peptide with a high avidity. The hybridoma effectively recognized virus variants and targeted cells with low HLA-A2 expression, which has not been reported previously. Importantly, high-avidity murine TCRs effectively redirected human non-HCV-specific T-lymphocytes to recognize human hepatoma cells with HCV RNA replication driven by a subgenomic HCV replicon. Taken together, TCR candidates with a range of functional avidities, which can be used to study immune recognition of HCV-positive targets, have been generated. This has implications for TCR-related immunotherapy against HCV.
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| 5. |
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| 6. |
- Mazzotti, L, et al.
(författare)
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T-Cell Receptor Repertoire Sequencing and Its Applications: Focus on Infectious Diseases and Cancer
- 2022
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 23:15
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Tidskriftsartikel (refereegranskat)abstract
- The immune system is a dynamic feature of each individual and a footprint of our unique internal and external exposures. Indeed, the type and level of exposure to physical and biological agents shape the development and behavior of this complex and diffuse system. Many pathological conditions depend on how our immune system responds or does not respond to a pathogen or a disease or on how the regulation of immunity is altered by the disease itself. T-cells are important players in adaptive immunity and, together with B-cells, define specificity and monitor the internal and external signals that our organism perceives through its specific receptors, TCRs and BCRs, respectively. Today, high-throughput sequencing (HTS) applied to the TCR repertoire has opened a window of opportunity to disclose T-cell repertoire development and behavior down to the clonal level. Although TCR repertoire sequencing is easily accessible today, it is important to deeply understand the available technologies for choosing the best fit for the specific experimental needs and questions. Here, we provide an updated overview of TCR repertoire sequencing strategies, providers and applications to infectious diseases and cancer to guide researchers’ choice through the multitude of available options. The possibility of extending the TCR repertoire to HLA characterization will be of pivotal importance in the near future to understand how specific HLA genes shape T-cell responses in different pathological contexts and will add a level of comprehension that was unthinkable just a few years ago.
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| 7. |
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| 8. |
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| 9. |
- Rodriguez, L. F., et al.
(författare)
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Limits to the magnetic field in the planetary nebula NGC 246 from faraday rotation
- 2017
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Ingår i: Revista Mexicana de Astronomia y Astrofisica. - 0185-1101. ; 53:1, s. 45-52
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Tidskriftsartikel (refereegranskat)abstract
- We present radio continuum observations of the linearly polarized extragalactic source J0047-1150, whose line of sight traverses the galactic planetary nebula NGC 246. We determine the position angle of the electric vector at seven frequencies between 1.3 and 1.8 GHz, finding no evidence of Faraday rotation and setting a 4-sigma upper limit to the rotation measure of 9.6 rad m(-2), which implies an upper limit to the average line-of-sight component of the magnetic field in NGC 246 of 1.3 mu G. However, we show that the rotation measure across a source with a dipolar magnetic field morphology practically cancels out. Therefore, if the magnetic field has this morphology, the local values of the magnetic field in NGC 246 could be much larger and will not be evident in a Faraday rotation experiment.
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| 10. |
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| 11. |
- Baldo, N, et al.
(författare)
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Calibration and Validation of a Visco-Elasto-Plastic Constitutive Model for Bituminous Conglomerates
- 2009
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Ingår i: ADVANCED TESTING AND CHARACTERISATION OF BITUMINOUS MATERIALS. - Rhodes, Greece : CRC Press. - 9780415558549 ; , s. 879-888
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Konferensbidrag (refereegranskat)abstract
- The paper presents and discusses the calibration and validation of a three-dimensional constitutive visco-elasto-plastic model developed for the analysis of the mechanical behaviour of bituminous mixes. The methodology, an inverse problem technique, uses a one-dimensional analytic formulation of the constitutive model and four different algorithms of non-linear constrained optimisation: the Conjugate Gradient, Montecarlo, Davidon-Fletcher-Powell and Simplex. On the basis of the creep recovery data obtained from an experiment in support of the model calibration, it was verified that the values of the constitutive parameters can be reliably identified, even starting from different initial guesses. A subsequent comparison between the experimental creep curves and numerical ones of the 3-D model demonstrated minimal shifts, confirming the robustness of the identification procedure for the parameters.
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| 15. |
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| 16. |
- Healy, K, et al.
(författare)
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Chronic Viral Liver Diseases: Approaching the Liver Using T Cell Receptor-Mediated Gene Technologies
- 2020
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Chronic infection with viral hepatitis is a major risk factor for liver injury and hepatocellular carcinoma (HCC). One major contributing factor to the chronicity is the dysfunction of virus-specific T cell immunity. T cells engineered to express virus-specific T cell receptors (TCRs) may be a therapeutic option to improve host antiviral responses and have demonstrated clinical success against virus-associated tumours. This review aims to give an overview of TCRs identified from viral hepatitis research and discuss how translational lessons learned from cancer immunotherapy can be applied to the field. TCR isolation pipelines, liver homing signals, cell type options, as well as safety considerations will be discussed herein.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Maravelia, P, et al.
(författare)
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Liquid Biopsy in Hepatocellular Carcinoma: Opportunities and Challenges for Immunotherapy
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:17
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Tidskriftsartikel (refereegranskat)abstract
- Hepatocellular carcinoma (HCC) is one of the deadliest cancer types worldwide. HCC is often diagnosed at a late stage when the therapeutic options are very limited. However, even at the earlier stages, the best treatment is liver transplantation, surgical resection or ablation. Surgical resection and ablation may carry a high risk of tumor recurrence. The recent introduction of immunotherapies resulted in clinical responses for a subgroup of patients, but there were still no effective predictive markers for response to immunotherapy or for recurrence after surgical therapy. The identification of biomarkers that could correlate and predict response or recurrence would require close monitoring of the patients throughout and after the completion of treatment. However, this would not be performed efficiently by repeated and invasive tissue biopsies. A better approach would be to use liquid biopsies including circulating tumor DNA (ctDNA), circulating RNA (e.g., microRNAs), circulating tumor cells (CTC) and extracellular vesicles (EVs) (e.g., exosomes) for disease monitoring in a non-invasive manner. In this review, we discuss the currently available technology that can enable the use of liquid biopsy as a diagnostic and prognostic tool. Moreover, we discuss the opportunities and challenges of the clinical application of liquid biopsy for immunotherapy of HCC.
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| 23. |
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| 24. |
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| 25. |
- Pasetto, A, et al.
(författare)
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Editorial: HBV-the naked truth?
- 2019
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Ingår i: Alimentary pharmacology & therapeutics. - : Wiley. - 1365-2036 .- 0269-2813. ; 50:8, s. 963-964
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 26. |
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| 27. |
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| 28. |
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| 29. |
- Pasetto, A, et al.
(författare)
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Single-Cell TCR and Transcriptome Analysis: An Indispensable Tool for Studying T-Cell Biology and Cancer Immunotherapy
- 2021
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 689091-
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Tidskriftsartikel (refereegranskat)abstract
- T cells have been known to be the driving force for immune response and cancer immunotherapy. Recent advances on single-cell sequencing techniques have empowered scientists to discover new biology at the single-cell level. Here, we review the single-cell techniques used for T-cell studies, including T-cell receptor (TCR) and transcriptome analysis. In addition, we summarize the approaches used for the identification of T-cell neoantigens, an important aspect for T-cell mediated cancer immunotherapy. More importantly, we discuss the applications of single-cell techniques for T-cell studies, including T-cell development and differentiation, as well as the role of T cells in autoimmunity, infectious disease and cancer immunotherapy. Taken together, this powerful tool not only can validate previous observation by conventional approaches, but also can pave the way for new discovery, such as previous unidentified T-cell subpopulations that potentially responsible for clinical outcomes in patients with autoimmunity or cancer.
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| 30. |
- Pasetto, A, et al.
(författare)
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T-Cell Repertoire Characterization
- 2022
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Ingår i: Methods in molecular biology (Clifton, N.J.). - New York, NY : Springer US. - 1940-6029. ; 2574, s. 209-219
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Tidskriftsartikel (refereegranskat)
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| 31. |
- Pasetto, A, et al.
(författare)
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TCR-redirected human T cells inhibit hepatitis C virus replication: hepatotoxic potential is linked to antigen specificity and functional avidity
- 2012
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 189:9, s. 4510-4519
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Tidskriftsartikel (refereegranskat)abstract
- Virus-specific CTL with high levels of functional avidity have been associated with viral clearance in hepatitis C virus (HCV) infection and with enhanced protective immunity. In chronic HCV infection, lack of antiviral CTL is frequently observed. In this study, we aim to investigate novel HCV TCRs that differ in Ag specificity. This involved isolating new HCV-specific murine TCRs that recognize a conserved HLA-A2–restricted CTL epitope within the nonstructural protein (NS) 5A viral protein and comparing them with TCRs recognizing another conserved CTL target in the NS3 viral protein. This was done by expressing the TCRs in human T cells and analyzing the function of the resulting TCR-transduced T cells. Our result indicates that these TCRs are efficiently assembled in transduced human T cells. They recognize peptide-loaded targets and demonstrate polyfunctional features such as IL-2, IFN-γ, and TNF-α secretion. However, in contrast to NS3-specific TCRs, the NS5A TCR-transduced T cells consist of a smaller proportion of polyfunctional T cells and require more peptide ligands to trigger the effector functions, including degranulation. Despite the differences, NS5A TCRs show effective inhibition of HCV replication in human hepatoma cells with persistent HCV RNA replication. Moreover, cellular injury demonstrated by aspartate aminotransferase release and cell death is less significant in the hepatoma cells following coincubation with NS5A TCR-transduced T cells, which is a property consistent with noncytotoxic antiviral CTLs. Our results suggest that HCV TCR-transduced T cells may be promising for the treatment of patients with chronic HCV infections.
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| 32. |
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Silva, DN, et al.
(författare)
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Process Development for Adoptive Cell Therapy in Academia: A Pipeline for Clinical-Scale Manufacturing of Multiple TCR-T Cell Products
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 896242-
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Tidskriftsartikel (refereegranskat)abstract
- Cellular immunotherapies based on T cell receptor (TCR) transfer are promising approaches for the treatment of cancer and chronic viral infections. The discovery of novel receptors is expanding considerably; however, the clinical development of TCR-T cell therapies still lags. Here we provide a pipeline for process development and clinical-scale manufacturing of TCR-T cells in academia. We utilized two TCRs specific for hepatitis C virus (HCV) as models because of their marked differences in avidity and functional profile in TCR-redirected cells. With our clinical-scale pipeline, we reproduced the functional profile associated with each TCR. Moreover, the two TCR-T cell products demonstrated similar yield, purity, transduction efficiency as well as phenotype. The TCR-T cell products had a highly reproducible yield of over 1.4 × 109 cells, with an average viability of 93%; 97.8–99% of cells were CD3+, of which 47.66 ± 2.02% were CD8+ T cells; the phenotype was markedly associated with central memory (CD62L+CD45RO+) for CD4+ (93.70 ± 5.23%) and CD8+ (94.26 ± 4.04%). The functional assessments in 2D and 3D cell culture assays showed that TCR-T cells mounted a polyfunctional response to the cognate HCV peptide target in tumor cell lines, including killing. Collectively, we report a solid strategy for the efficient large-scale manufacturing of TCR-T cells.
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| 37. |
- Stasiuk, A. V., et al.
(författare)
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Influence of structure and nature of pseudo-poly(amino acid)s on size and morphology of their particle in self-stabilized aqueous dispersions
- 2023
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Ingår i: Applied Nanoscience. - Germany : Springer. - 2190-5509 .- 2190-5517. ; 13:7, s. 5011-5019
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Tidskriftsartikel (refereegranskat)abstract
- Polyester pseudo-poly(amino acid)s due to their biodegradability and biocompatibility are promising materials for the development of dispersed systems for drug delivery. It is essential for drug delivery systems to reach the target site within a certain period before they are eliminated or degraded. Biodegradable materials should meet the following criteria: (1) possess surface-active properties; (2) be non-toxic; (3) form self-stabilized dispersions with the size of the dispersed phase in the range of 10–100 nm. Polyesters based on N-derivatives of dicarboxylic α-amino acids and hydrophilic PEG diols modified with phosphate group meet the requirements to the dispersed drug delivery systems. Obtained polyesters have a complex architecture consisting of hydrophilic fragments, which stabilize the system, and lipophilic fragments, which solubilize biologically active substances. The phosphate group introduced into the hydrophilic chain of polyoxyethylene glycol provides chemisorption of a number of biologically active substances due to the formation of ionic bonds between them. Synthesized polyesters form self-stabilized dispersed systems, which do not require additional stabilizing agents when used for medical applications.
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| 39. |
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