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https://www.readbyqxmd.com/read/28339457/targeted-aav5-smad7-gene-therapy-inhibits-corneal-scarring-in-vivo
#1
Suneel Gupta, Jason T Rodier, Ajay Sharma, Elizabeth A Giuliano, Prashant R Sinha, Nathan P Hesemann, Arkasubhra Ghosh, Rajiv R Mohan
Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring...
2017: PloS One
https://www.readbyqxmd.com/read/28331526/impaired-human-immunodeficiency-virus-type-1-replicative-fitness-in-atypical-viremic-non-progressor-individuals
#2
Jan Weber, Richard M Gibson, Lenka Sácká, Dmytro Strunin, Jan Hodek, Jitka Weberová, Marcela Pávová, David J Alouani, Robert Asaad, Benigno Rodriguez, Michael M Lederman, Miguel E Quiñones-Mateu
BACKGROUND: Progression rates from initial HIV-1 infection to advanced AIDS vary significantly among infected individuals. A distinct subgroup of HIV-1-infected individuals-termed viremic non-progressors (VNP) or controllers-do not seem to progress to AIDS, maintaining high CD4(+) T cell counts despite high levels of viremia for many years. Several studies have evaluated multiple host factors, including immune activation, trying to elucidate the atypical HIV-1 disease progression in these patients; however, limited work has been done to characterize viral factors in viremic controllers...
2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28331122/an-autopsy-case-report-of-adult-t-cell-leukemia-accompanied-by-rheumatoid-arthritis-mimicking-diffuse-panbronchiolitis
#3
Tomoko Shiraishi, Hiroshi Ishimoto, Kentaro Akata, Toshinori Kawanami, Kazuhiro Yatera, Hiroshi Mukae
A 50-year-old female with a history of chronic sinusitis and rheumatoid arthritis visited our department with repetitive lower respiratory tract infections of Pseudomonas aeruginosa. Her chest CT showed diffuse panbronchiolitis-like pulmonary lesions, her blood examination revealed atypical lymphocytes, and she was serologically positive for anti-human T-lymphotrophic virus type 1 (HTLV-1) antibody. Her rheumatoid arthritis had been well-controlled after biological agent treatment followed by anti-inflammatory analgesic treatment...
2017: Journal of UOEH
https://www.readbyqxmd.com/read/28330473/dynamic-and-specific-immune-responses-against-multiple-tumor-antigens-were-elicited-in-patients-with-hepatocellular-carcinoma-after-cell-based-immunotherapy
#4
Yanyan Han, Yeting Wu, Chou Yang, Jing Huang, Yabing Guo, Li Liu, Ping Chen, Dongyun Wu, Junyun Liu, Jin Li, Xiangjun Zhou, Jinlin Hou
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in China and frequently occurs with chronic hepatitis B virus infection. To investigate whether cell-based cancer immunotherapy induces tumor specific immune responses in patients with HCC and provides clinical benefits, as well as to elucidate the most immunogenic tumor associated antigens (TAAs), multiple antigen stimulating cellular therapy (MASCT) was applied in addition to standard of care. METHODS: Mature dendritic cells (DCs) and activated T cells prepared for MASCT were generated from autologous peripheral blood mononuclear cells (PBMCs)...
March 22, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28330372/car-t-cell-therapy-progress-and-prospects
#5
Olivia Wilkins, Allison May Keeler, Terence R Flotte
Lentivirus-mediated transduction of autologous T-cells with a chimeric antigen receptor (CAR) to confer a desired epitope-specificity as a targeted immunotherapy for cancer has been among the first human gene therapy techniques to demonstrate widespread therapeutic efficacy. Other approaches to using gene therapy to enhance anti-tumor immunity have been less specific and less effective. These included amplification, marking, and cytokine transduction of tumor infiltrating lymphocytes (TIL), recombinant virus-based expression of tumor antigens as a tumor vaccine, and transduction of antigen-presenting cells (APCs) with tumor antigens...
March 23, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28328934/proviruses-with-identical-sequences-comprise-a-large-fraction-of-the-replication-competent-hiv-reservoir
#6
John K Bui, Michele D Sobolewski, Brandon F Keele, Jonathan Spindler, Andrew Musick, Ann Wiegand, Brian T Luke, Wei Shao, Stephen H Hughes, John M Coffin, Mary F Kearney, John W Mellors
The major obstacle to curing HIV infection is the persistence of cells with intact proviruses that can produce replication-competent virus. This HIV reservoir is believed to exist primarily in CD4+ T-cells and is stable despite years of suppressive antiretroviral therapy. A potential mechanism for HIV persistence is clonal expansion of infected cells, but how often such clones carry replication-competent proviruses has been controversial. Here, we used single-genome sequencing to probe for identical HIV sequence matches among viruses recovered in different viral outgrowth cultures and between the sequences of outgrowth viruses and proviral or intracellular HIV RNA sequences in uncultured blood mononuclear cells from eight donors on suppressive ART with diverse proviral populations...
March 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28326624/current-status-of-clinical-trials-assessing-oncolytic-virus-therapy-for-urological-cancers
#7
REVIEW
Satoru Taguchi, Hiroshi Fukuhara, Yukio Homma, Tomoki Todo
Oncolytic virus therapy has recently been recognized as a promising new option for cancer treatment. Oncolytic viruses replicate selectively in cancer cells, thus killing them without harming normal cells. Notably, T-VEC (talimogene laherparepvec, formerly called OncoVEX(GM)(-)(CSF) ), an oncolytic herpes simplex virus type 1, was approved by the US Food and Drug Administration for the treatment of inoperable melanoma in October 2015, and was subsequently approved in Europe and Australia in 2016. The efficacies of many types of oncolytic viruses against urological cancers have been investigated in preclinical studies during the past decade, and some have already been tested in clinical trials...
March 21, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28326304/hiv-diagnosis-and-treatment-through-advanced-technologies
#8
REVIEW
Hafiza Fizzah Zulfiqar, Aneeqa Javed, Sumbal, Bakht Afroze, Qurban Ali, Khadija Akbar, Tariq Nadeem, Muhammad Adeel Rana, Zaheer Ahmad Nazar, Idrees Ahmad Nasir, Tayyab Husnain
Human immunodeficiency virus (HIV) is the chief contributor to global burden of disease. In 2010, HIV was the fifth leading cause of disability-adjusted life years in people of all ages and leading cause for people aged 30-44 years. It is classified as a member of the family Retroviridae and genus Lentivirus based on the biological, morphological, and genetic properties. It infects different cells of the immune system, such as CD4+ T cells (T-helper cells), dendritic cells, and macrophages. HIV has two subtypes: HIV-1 and HIV-2...
2017: Frontiers in Public Health
https://www.readbyqxmd.com/read/28322598/screening-and-functional-profiling-of-small-molecule-hiv-1-entry-and-fusion-inhibitors
#9
Charline Giroud, Yuhong Du, Mariana Marin, Qui Min, Nathan T Jui, Haian Fu, Gregory B Melikyan
HIV-1 entry and fusion with target cells is an important target for antiviral therapy. However, a few currently approved treatments are not effective as monotherapy due to the emergence of drug resistance. This consideration has fueled efforts to develop new bioavailable inhibitors targeting different steps of the HIV-1 entry process. Here, a high-throughput screen was performed of a large library of 100,000 small molecules for HIV-1 entry/fusion inhibitors, using a direct virus-cell fusion assay in a 384 half-well format...
February 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28320417/impaired-human-immunodeficiency-virus-type-1-replicative-fitness-in-atypical-viremic-non-progressor-individuals
#10
Jan Weber, Richard M Gibson, Lenka Sácká, Dmytro Strunin, Jan Hodek, Jitka Weberová, Marcela Pávová, David J Alouani, Robert Asaad, Benigno Rodriguez, Michael M Lederman, Miguel E Quiñones-Mateu
BACKGROUND: Progression rates from initial HIV-1 infection to advanced AIDS vary significantly among infected individuals. A distinct subgroup of HIV-1-infected individuals-termed viremic non-progressors (VNP) or controllers-do not seem to progress to AIDS, maintaining high CD4(+) T cell counts despite high levels of viremia for many years. Several studies have evaluated multiple host factors, including immune activation, trying to elucidate the atypical HIV-1 disease progression in these patients; however, limited work has been done to characterize viral factors in viremic controllers...
March 20, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28319449/non-clinical-study-examining-aav8-tbg-hldlr-vector-associated-toxicity-in-chow-fed-wild-type-and-ldlr-rhesus-macaques
#11
Jenny A Greig, Maria P Limberis, Peter Bell, Shu-Jen Chen, Roberto Calcedo, Daniel J Rader, James M Wilson
Vectors based on adeno-associated virus serotype 8 (AAV8) have been evaluated in several clinical trials of gene therapy for hemophilia B with encouraging results. In preparation for a Phase 1 clinical trial of AAV8 gene therapy for the treatment of homozygous familial hypercholesterolemia (HoFH), the safety of the clinical candidate vector, AAV8.TBG.hLDLR, was evaluated in wild-type rhesus macaques and macaques heterozygous for a nonsense mutation in the low-density lipoprotein receptor (LDLR) gene (LDLR(+/-))...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28319448/rationale-and-design-of-a-phase-1-clinical-trial-to-evaluate-hsv-g207-alone-or-with-a-single-radiation-dose-in-children-with-progressive-or-recurrent-malignant-supratentorial-brain-tumors
#12
Alicia M Waters, James M Johnston, Alyssa T Reddy, John Fiveash, Avi Madan-Swain, Kara Kachurak, Asim K Bag, G Yancey Gillespie, James M Markert, Gregory K Friedman
Primary central nervous system tumors are the most common solid neoplasm of childhood and the leading cause of cancer-related death in pediatric patients. Survival rates for children with malignant supratentorial brain tumors are poor despite aggressive treatment with combinations of surgery, radiation, and chemotherapy, and survivors often suffer from damaging lifelong sequelae from current therapies. Novel innovative treatments are greatly needed. One promising new approach is the use of a genetically engineered, conditionally replicating herpes simplex virus (HSV) that has shown tumor-specific tropism and potential efficacy in the treatment of malignant brain tumors...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28318036/autophagy-determines-efficiency-of-liver-directed-gene-therapy-with-adeno-associated-viral-vectors
#13
Marianna Hösel, Anke Huber, Susanne Bohlen, Julie Lucifora, Giuseppe Ronzitti, Francesco Puzzo, Florence Boisgerault, Ulrich T Hacker, Wilhelmus J Kwanten, Nora Klöting, Matthias Blüher, Alexander Gluschko, Michael Schramm, Olaf Utermöhlen, Wilhelm Bloch, Federico Mingozzi, Oleg Krut, Hildegard Büning
Use of Adeno-associated viral (AAV) vectors for liver-directed gene therapy has shown considerable success, particularly in patients with severe hemophilia B. However, the high vector doses required to reach therapeutic levels of transgene expression caused liver inflammation in some patients that selectively destroyed transduced hepatocytes. We hypothesized that such detrimental immune responses can be avoided by enhancing the efficacy of AAV vectors in hepatocytes. Because autophagy is a key liver response to environmental stresses, we characterized the impact of hepatic autophagy on AAV infection...
March 20, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28314785/tumor-localized-secretion-of-soluble-pd1-enhances-oncolytic-virotherapy
#14
Mee Y Bartee, Katherine M Dunlap, Eric Bartee
Oncolytic virotherapy represents an attractive option for the treatment of a variety of aggressive or refractory tumors. While this therapy is effective at rapidly debulking directly injected tumor masses, achieving complete eradication of established disease has proven difficult. One method to overcome this challenge is to use oncolytic viruses to induce secondary anti-tumor immune responses. Unfortunately, while the initial induction of these immune responses is typically robust, their subsequent efficacy is often inhibited through a variety of immunoregulatory mechanisms, including the PD1/PDL1 T-cell checkpoint pathway...
March 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28303793/prediction-of-the-containment-of-hiv-infection-by-antiretroviral-therapy-a-variable-structure-control-approach
#15
Anet J N Anelone, Sarah K Spurgeon
It is demonstrated that the reachability paradigm from variable structure control theory is a suitable framework to monitor and predict the progression of the human immunodeficiency virus (HIV) infection following initiation of antiretroviral therapy (ART). A manifold is selected which characterises the infection-free steady-state. A model of HIV infection together with an associated reachability analysis is used to formulate a dynamical condition for the containment of HIV infection on the manifold. This condition is tested using data from two different HIV clinical trials which contain measurements of the CD4+ T cell count and HIV load in the peripheral blood collected from HIV infected individuals for the six month period following initiation of ART...
February 2017: IET Systems Biology
https://www.readbyqxmd.com/read/28301970/disclosing-the-parameters-leading-to-high-productivity-of-retroviral-producer-cells-lines-evaluating-random-vs-targeted-integration
#16
Vanessa Sofia Bandeira, Hélio A Tomás, Evren Alici, Manuel J C T Carrondo, Ana Sofia Coroadinha
Gammaretrovirus and lentivirus are the preferred viral vectors to genetically modify T- and NK- cells to be used in immune-cell therapies. The transduction efficiency of hematopoietic and T cells is more efficient using Gibbon ape leukemia virus (GaLV) pseudotyping. In this context gammaretroviral vector producer cells offer competitive higher titers than transient lentiviral vectors productions. The main aim of this work was to identify the key parameters governing GalV pseudotyped gammaretroviral vector productivity in stable producer cells using a retroviral vector expression cassette enabling positive (facilitating cell enrichment) and negative cell selection (allowing cell elimination)...
March 16, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28298605/cxcr5-dependent-entry-of-cd8-t-cells-into-rhesus-macaque-b-cell-follicles-achieved-through-t-cell-engineering
#17
Victor I Ayala, Claire Deleage, Matthew T Trivett, Sumiti Jain, Lori V Coren, Matthew W Breed, Joshua A Kramer, James A Thomas, Jacob D Estes, Jeffrey D Lifson, David E Ott
Follicular helper CD4 T cells, TFH, residing in B-cell follicles within secondary lymphoid tissues, are readily infected by AIDS viruses and are a major source of persistent virus despite relative control of viral replication. This persistence is due at least in part to a relative exclusion of effective antiviral CD8 T cells from B-cell follicles. To determine whether CD8 T cells could be engineered to enter B-cell follicles, we genetically modified unselected CD8 T cells to express CXCR5, the chemokine receptor implicated in cellular entry into B-cell follicles...
March 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28295463/immune-phenotype-and-function-of-nk-and-t-cells-in-chronic-hepatitis-c-patients-who-received-a-single-dose-of-anti-mir-122-rg-101
#18
Femke Stelma, Meike H van der Ree, Marjan J Sinnige, Anthony Brown, Leo Swadling, J Marleen L de Vree, Sophie B Willemse, Marc van der Valk, Paul Grint, Steven Neben, Paul Klenerman, Eleanor Barnes, Neeltje A Kootstra, Hendrik W Reesink
MicroRNA-122 (miR-122) is an important host factor for the hepatitis C (HCV) virus. Treatment with RG-101, a GalNAc conjugated anti-miR-122 oligonucleotide, resulted in a significant viral load reduction in patients with chronic hepatitis C (CHC) infection. Here, we analyzed the effects of RG-101 therapy on antiviral immunity. 32 CHC patients HCV genotype 1, 3 and 4 received a single subcutaneous administration with RG-101 at 2 mg/kg (n=14), 4 mg/kg (n=14) or placebo (n=2 per dosing group). Plasma and PBMCs were collected at multiple time points and comprehensive immunological analyses were performed...
March 11, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28289286/early-antibody-therapy-can-induce-long-lasting-immunity-to-shiv
#19
Yoshiaki Nishimura, Rajeev Gautam, Tae-Wook Chun, Reza Sadjadpour, Kathryn E Foulds, Masashi Shingai, Florian Klein, Anna Gazumyan, Jovana Golijanin, Mitzi Donaldson, Olivia K Donau, Ronald J Plishka, Alicia Buckler-White, Michael S Seaman, Jeffrey D Lifson, Richard A Koup, Anthony S Fauci, Michel C Nussenzweig, Malcolm A Martin
Highly potent and broadly neutralizing anti-HIV-1 antibodies (bNAbs) have been used to prevent and treat lentivirus infections in humanized mice, macaques, and humans. In immunotherapy experiments, administration of bNAbs to chronically infected animals transiently suppresses virus replication, which invariably returns to pre-treatment levels and results in progression to clinical disease. Here we show that early administration of bNAbs in a macaque simian/human immunodeficiency virus (SHIV) model is associated with very low levels of persistent viraemia, which leads to the establishment of T-cell immunity and resultant long-term infection control...
March 13, 2017: Nature
https://www.readbyqxmd.com/read/28289079/deletion-of-f4l-ribonucleotide-reductase-in-vaccinia-virus-produces-a-selective-oncolytic-virus-and-promotes-anti-tumor-immunity-with-superior-safety-in-bladder-cancer-models
#20
Kyle G Potts, Chad R Irwin, Nicole A Favis, Desmond B Pink, Krista M Vincent, John D Lewis, Ronald B Moore, Mary M Hitt, David H Evans
Bladder cancer has a recurrence rate of up to 80% and many patients require multiple treatments that often fail, eventually leading to disease progression. In particular, standard of care for high-grade disease, Bacillus Calmette-Guérin (BCG), fails in 30% of patients. We have generated a novel oncolytic vaccinia virus (VACV) by mutating the F4L gene that encodes the virus homolog of the cell-cycle-regulated small subunit of ribonucleotide reductase (RRM2). The F4L-deleted VACVs are highly attenuated in normal tissues, and since cancer cells commonly express elevated RRM2 levels, have tumor-selective replication and cell killing...
March 13, 2017: EMBO Molecular Medicine
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