TCR gene-modified T cells can efficiently treat established hepatitis C-associated hepatocellular carcinoma tumors

Abstract The success in recent clinical trials using T cell receptor (TCR)-genetically engineered T cells to treat melanoma has encouraged the use of this approach toward other malignancies and viral infections. Although hepatitis C virus (HCV) infection is being treated with a new set of successful direct anti-viral agents, potential for virologic breakthrough or relapse by immune escape variants remains. Additionally, many HCV+ patients have HCV-associated disease, including hepatocellular carcinoma (HCC), which does not respond to these novel drugs. Further exploration of other approaches to address HCV infection and its associated disease are highly warranted. Here, we demonstrate the therapeutic potential of PBL-derived T cells genetically engineered with a high-affinity, HLA-A2-restricted, HCV NS3:1406-1415-reactive TCR. HCV1406 TCR-transduced T cells can recognize naturally processed antigen and elicit CD8-independent recognition of both peptide-loaded targets and HCV+ human HCC cell lines. Furthermore, these cells can mediate regression of established HCV+ HCC in vivo. Our results suggest that HCV TCR-engineered antigen-reactive T cells may be a plausible immunotherapy option to treat HCV-associated malignancies, such as HCC.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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CONCLUSION: Patients with non-cancer symptoms are frequently referred with suspected cancer. Patients with red flag symptoms are not aware of their significance and they have low expectations of healthcare. PMID: 31439066 [PubMed - as supplied by publisher]
Source: Journal of Laryngology and Otology - Category: ENT & OMF Tags: J Laryngol Otol Source Type: research
Publication date: 15 October 2019Source: Biosensors and Bioelectronics, Volume 143Author(s): Jinyang Chen, Yan Wu, Cuicui Fu, Haiyan Cao, Xiaoping Tan, Wenbing Shi, Zhaoyang WuAbstractMicroRNAs (miRNAs) serve as significant regulators in a variety of diseases and have been emerging as a class of promising biomarkers for early cancer diagnosis. Herein, an enzyme-free surface-enhanced Raman scattering (SERS) platform was proposed for sensitive and reliable detection of target miRNA-21 using a corrective internal standard (IS)-based ratiometric SERS probe coupled with mismatched catalytic hairpin assembly (CHA) amplification....
Source: Biosensors and Bioelectronics - Category: Biotechnology Source Type: research
Publication date: 15 October 2019Source: Biosensors and Bioelectronics, Volume 143Author(s): Moslem Afzali, Ali Mostafavi, Tayebeh ShamspurAbstractDespite its useful properties, imiquimod (IMQ), known as an anti-cancer drug, can be harmful to the skin at high concentrations. Therefore, we have developed a novel electrochemical sensor to determine IMQ, for the first time. A glassy carbon electrode (GCE) was modified by a new composite comprising of ionic liquid-based molecularly imprinted polymer (MIP) and gold nanoparticles/graphene oxide (Au/GO). The MIP/Au/GO nanocomposite was synthesized through non-covalent imprinting ...
Source: Biosensors and Bioelectronics - Category: Biotechnology Source Type: research
Publication date: Available online 23 August 2019Source: MethodsAuthor(s): Jianji Chen, Cari Sagum, Mark T BedfordAbstractSignal transduction is driven by protein interactions that are controlled by posttranslational modifications (PTM). Usually, protein domains are responsible for “reading” the PTM signal deposited on the interacting partners. Protein domain microarrays have been developed as a high throughput platform to facilitate the rapid identification of protein-protein interactions, and this approach has become broadly used in biomedical research. In this review, we will summarize the history, developme...
Source: Methods - Category: Molecular Biology Source Type: research
Publication date: 5 January 2020Source: Journal of Molecular Structure, Volume 1199Author(s): Di Wu, Liang Guo, Si-Jie LiAbstractTwo Schiff base ligands 2-((ethylamino)methyl)-6-methoxyphenol (HL1) and (E)-2-(((2-(dimethylamino)ethyl)imino)methyl)-6-methoxyphenol (HL2) with bi-nucleating or tri-nucleating mode have been successfully prepared via an one step organic condensation reaction, which were further applied in the synthesis of three new Cu(II) and Ni(II)-based coordination complexes [Cu(L1)2](EtOH) (1), [Ni(L1)2](EtOH) (2) and [Cu(L2)(HL2)(SCN)](MeOH)2 (3). Furthermore, a hand grinding technique has been used to dec...
Source: Journal of Molecular Structure - Category: Molecular Biology Source Type: research
This study was done by collecting wild PU and cultivated PU and compared with a counterfeit which is commonly found in the market. Fourier Transform Infrared (FTIR) and Two-Dimension Infrared (2DIR) for the qualitative analysis are often regarded as green methods because the original resources of the test sample are preserved. The different spectral patterns of the counterfeit PU compared with the genuine PU were clearly indicated in 1D FTIR spectrum. The 2DIR spectrum of counterfeit PU showed more than 70% dissimilarity compared to genuine PU. This rapid and simple sample preparation enhances the speed of qualitative anal...
Source: Journal of Molecular Structure - Category: Molecular Biology Source Type: research
Publication date: 15 December 2019Source: Journal of Molecular Structure, Volume 1198Author(s): Yu-Ying Tian, Zhi-Guo Xin, Hai-Feng Hou, Xiao-Chun Zhu, Qian Guo, Qin XiaoAbstractTwo new Cu(II)-containing coordination complexes with the chemical formulae of [Cu2(pydc)2(H2O)2]n (1, pydc = 3,5-pyridinedicarboxylate) and {[Cu(H2O)2(H3hmidc)2](H2O)}n (2, H4hmidc = 2-(hydroxymethyl)-1H-imidazole-4,5-dicarboxylic acid) have been successfully synthesized and characterized under solvothermal conditions. The in vitro anti-tumor activities of compounds 1 and 2 were studied on human atrial myxoma cell HemECs. The WST-8 as...
Source: Journal of Molecular Structure - Category: Molecular Biology Source Type: research
In this study; spectroscopic, electronic and biological properties of Boc-D-Lys-OH (BDLO) molecule have been examined using quantum chemical calculations. First of all, the molecule was optimized and geometric structure parameters and vibrational wavenumbers were calculated by DFT/ B3LYP methods 6-311G++(d,p) basis set. The calculated wavenumbers were then compared with the experimental values of the FT-IR and FT-Raman spectra. Finally, the molecular docking was determined for anti apoptotic proteins with BDLO molecule. The results showed Boc-D-Lys-OH molecule had more binding affinity with AKT1 and concluded this molecule...
Source: Journal of Molecular Structure - Category: Molecular Biology Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Gulcin Tezcan1, Ekaterina V. Martynova1, Zarema E. Gilazieva1, Alan McIntyre2, Albert A. Rizvanov1 and Svetlana F. Khaiboullina1,3* 1Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia 2Centre for Cancer Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, United Kingdom 3Department of Microbiology and Immunology, University of Nevada, Reno, Reno, NV, United States Inflammation has a crucial role in protection against various pathogens. The inflammasome is an intracellular multiprotein signaling complex that is linked to pathogen sensing and...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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