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https://www.readbyqxmd.com/read/28813430/reprogramming-human-gallbladder-cells-into-insulin-producing-%C3%AE-like-cells
#1
Feorillo Galivo, Eric Benedetti, Yuhan Wang, Carl Pelz, Jonathan Schug, Klaus H Kaestner, Markus Grompe
The gallbladder and cystic duct (GBCs) are parts of the extrahepatic biliary tree and share a common developmental origin with the ventral pancreas. Here, we report on the very first genetic reprogramming of patient-derived human GBCs to β-like cells for potential autologous cell replacement therapy for type 1 diabetes. We developed a robust method for large-scale expansion of human GBCs ex vivo. GBCs were reprogrammed into insulin-producing pancreatic β-like cells by a combined adenoviral-mediated expression of hallmark pancreatic endocrine transcription factors PDX1, MAFA, NEUROG3, and PAX6 and differentiation culture in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28810803/driving-cars-on-the-highway-to-solid-cancer-some-considerations-on-the-adoptive-therapy-with-car-t-cells
#2
Hinrich Abken
Adoptive therapy with chimeric antigen receptor (CAR) redirected T cells achieved lasting remissions in hematologic malignancies even in terminal stages of the disease; exploring CAR T cell therapy in the treatment of solid tumors has just begun, balancing efficacy versus toxicity in early phase trials. In contrast to leukemia/lymphoma, solid tumors display a tremendously variable biology demanding different strategies to make a T cell attack successful in the long-term. We summarize current developments, discuss the hurdles and consider some modifications to improve the CAR T cell therapy in the treatment of solid tumors...
August 16, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28809608/treatment-of-patients-with-metastatic-cancer-using-a-major-histocompatibility-complex-class-ii-restricted-t-cell-receptor-targeting-the-cancer-germline-antigen-mage-a3
#3
Yong-Chen Lu, Linda L Parker, Tangying Lu, Zhili Zheng, Mary Ann Toomey, Donald E White, Xin Yao, Yong F Li, Paul F Robbins, Steven A Feldman, Pierre van der Bruggen, Christopher A Klebanoff, Stephanie L Goff, Richard M Sherry, Udai S Kammula, James C Yang, Steven A Rosenberg
Purpose Adoptive transfer of genetically modified T cells is being explored as a treatment for patients with metastatic cancer. Most current strategies use genes that encode major histocompatibility complex (MHC) class I-restricted T-cell receptors (TCRs) or chimeric antigen receptors to genetically modify CD8(+) T cells or bulk T cells for treatment. Here, we evaluated the safety and efficacy of an adoptive CD4(+) T-cell therapy using an MHC class II-restricted, HLA-DPB1*0401-restricted TCR that recognized the cancer germline antigen, MAGE-A3 (melanoma-associated antigen-A3)...
August 15, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28809089/inverted-quasi-spherical-droplets-on-polydopamine-tio2-substrates-for-enhancing-gene-delivery
#4
Seung-Hyun Kim, Mihyun Lee, Mira Cho, Il-Sun Kim, Kook In Park, Haeshin Lee, Jae-Hyung Jang
Devising efficient gene delivery systems is crucial to enhancing the therapeutic efficacy of gene-cell therapy approaches. Herein, inverted quasi-spherical (iQS) droplet systems, which enhance gene delivery efficiencies by reducing the path lengths of gene vectors, mediating motions of vectors at early stages, and raising the contact frequencies of vectors with cells, are developed by adopting the principle of 3D hanging-drop cell culture. Micrometer-sized polydopamine (pDA) holes are created on superhydrophobic titanium isopropoxide (TiO2 )-coated substrates by physical scraping; droplets are loaded on the pDA holes, and inversion of the substrate generates iQS droplets with large contact angles...
August 15, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/28807232/ovarian-cancer-novel-molecular-aspects-for-clinical-assessment
#5
REVIEW
Raffaele Palmirotta, Erica Silvestris, Stella D'Oronzo, Angela Cardascia, Franco Silvestris
Ovarian cancer is a very heterogeneous tumor which has been traditionally characterized according to the different histological subtypes and differentiation degree. In recent years, innovative molecular screening biotechnologies have allowed to identify further subtypes of this cancer based on gene expression profiles, mutational features, and epigenetic factors. These novel classification systems emphasizing the molecular signatures within the broad spectrum of ovarian cancer have not only allowed a more precise prognostic prediction, but also proper therapeutic strategies for specific subgroups of patients...
September 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28805581/nonmotor-parkinson-s-and-future-directions
#6
Nataliya Titova, K Ray Chaudhuri
Nonmotor symptoms (NMS) of Parkinson's disease (PD) are integral to the condition largely regarded as a motor syndrome. A range of NMS underpin the prodromal stage of Parkinson's and are present with variable frequency, range, and nature across the whole journey of a patient with Parkinson's from the onset of the motor disease to palliative stage. These symptoms also are key determinants of quality of life of the patient as well as the carer. Despite this, recognition management and focused treatment of NMS of PD remain poor...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28804488/anti-adhesion-therapies-in-inflammatory-bowel-disease-molecular-and-clinical-aspects
#7
REVIEW
Sebastian Zundler, Emily Becker, Carl Weidinger, Britta Siegmund
The number of biologicals for the therapy of immunologically mediated diseases is constantly growing. In contrast to other agents that were previously introduced in rheumatologic or dermatologic diseases and only later adopted for the treatment of inflammatory bowel diseases (IBDs), the field of IBD was ground breaking for the concept of anti-adhesion blockade. Anti-adhesion antibodies selectively target integrins controlling cell homing to the intestine, which leads to reduction of inflammatory infiltration to the gut in chronic intestinal inflammation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28801306/inducible-activation-of-myd88-and-cd40-in-car-t-cells-results-in-controllable-and-potent-antitumor-activity-in-preclinical-solid-tumor-models
#8
Melinda Mata, Claudia Gerken, Phuong Nguyen, Giedre Krenciute, David M Spencer, Stephen Gottschalk
Adoptive immunotherapy with T-cells expressing chimeric antigen receptors (CARs) has had limited success for solid tumors in early phase clinical studies. We reasoned that introducing into CAR T-cells an inducible co-stimulatory (iCO) molecule consisting of a chemical inducer of dimerization (CID)-binding domain and the MyD88 and CD40 signaling domains would improve and control CAR T-cell activation. In the presence of CID, T-cells expressing HER2-CARζ and a MyD88/CD40-based iCO molecule (HER2ζ.iCO T-cells) had superior T-cell proliferation, cytokine production, and ability to sequentially kill targets in vitro relative to HER2ζ...
August 11, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28797612/decentralized-manufacturing-of-cell-and-gene-therapies-overcoming-challenges-and-identifying-opportunities
#9
REVIEW
Richard P Harrison, Steven Ruck, Nicholas Medcalf, Qasim A Rafiq
Decentralized or "redistributed" manufacturing has the potential to revolutionize the manufacturing approach for cell and gene therapies (CGTs), moving away from the "Fordist" paradigm, delivering health care locally, customized to the end user and, by its very nature, overcoming many of the challenges associated with manufacturing and distribution of high volume goods. In departing from the traditional centralized model of manufacturing, decentralized manufacturing divides production across sites or geographic regions...
August 7, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28796151/potential-development-of-tumor-targeted-oral-anti-cancer-prodrugs-amino-acid-and-dipeptide-monoester-prodrugs-of-gemcitabine
#10
Yasuhiro Tsume, Adam J Drelich, David E Smith, Gordon L Amidon
One of the main obstacles for cancer therapies is to deliver medicines effectively to target sites. Since stroma cells are developed around tumors, chemotherapeutic agents have to go through stroma cells in order to reach tumors. As a method to improve drug delivery to the tumor site, a prodrug approach for gemcitabine was adopted. Amino acid and dipeptide monoester prodrugs of gemcitabine were synthesized and their chemical stability in buffers, resistance to thymidine phosphorylase and cytidine deaminase, antiproliferative activity, and uptake/permeability in HFF cells as a surrogate to stroma cells were determined and compared to their parent drug, gemcitabine...
August 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28794626/folic-acid-functionalized-polyethylenimine-superparamagnetic-iron-oxide-nanoparticles-as-theranostic-agents-for-magnetic-resonance-imaging-and-pd-l1-sirna-delivery-for-gastric-cancer
#11
Xin Luo, Xia Peng, Jingying Hou, Shuyun Wu, Jun Shen, Lingyun Wang
Programmed death ligand-1 (PD-L1), which is highly expressed in gastric cancers, interacts with programmed death-1 (PD-1) on T cells and is involved in T-cell immune resistance. To increase the therapeutic safety and accuracy of PD-1/PD-L1 blockade, RNA interference through targeted gene delivery was performed in our study. We developed folic acid (FA)- and disulfide (SS)-polyethylene glycol (PEG)-conjugated polyethylenimine (PEI) complexed with superparamagnetic iron oxide Fe3O4 nanoparticles (SPIONs) as a siRNA-delivery system for PD-L1 knockdown...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28792537/isolation-and-functional-characterization-of-hepatitis-b-virus-specific-t-cell-receptors-as-new-tools-for-experimental-and-clinical-use
#12
Karin Wisskirchen, Kai Metzger, Sophia Schreiber, Theresa Asen, Luise Weigand, Christina Dargel, Klaus Witter, Elisa Kieback, Martin F Sprinzl, Wolfgang Uckert, Matthias Schiemann, Dirk H Busch, Angela M Krackhardt, Ulrike Protzer
T-cell therapy of chronic hepatitis B is a novel approach to restore antiviral T-cell immunity and cure the infection. We aimed at identifying T-cell receptors (TCR) with high functional avidity that have the potential to be used for adoptive T-cell therapy. To this end, we cloned HLA-A*02-restricted, hepatitis B virus (HBV)-specific T cells from patients with acute or resolved HBV infection. We isolated 11 envelope- or core-specific TCRs and evaluated them in comprehensive functional analyses. T cells were genetically modified by retroviral transduction to express HBV-specific TCRs...
2017: PloS One
https://www.readbyqxmd.com/read/28791124/combining-dendritic-cells-and-b-cells-for-presentation-of-oxidised-tumour-antigens-to-cd8-t-cells
#13
Melanie L Grant, Nicholas Shields, Silke Neumann, Katrin Kramer, Andrea Bonato, Christopher Jackson, Margaret A Baird, Sarah L Young
The dendritic cell (DC) is the foremost antigen-presenting cell (APC) for ex vivo expansion of tumour-specific patient T cells. Despite marked responses in some patients following reinfusion of DC-activated autologous or HLA-matched donor T cells, overall response rates remain modest in solid tumours. Furthermore, most studies aim to generate immune responses against defined tumour-associated antigens (TAA), however, meta-analysis reveals that those approaches have less clinical success than those using whole tumour cells or their components...
July 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28783722/identification-of-essential-genes-for-cancer-immunotherapy
#14
Shashank J Patel, Neville E Sanjana, Rigel J Kishton, Arash Eidizadeh, Suman K Vodnala, Maggie Cam, Jared J Gartner, Li Jia, Seth M Steinberg, Tori N Yamamoto, Anand S Merchant, Gautam U Mehta, Anna Chichura, Ophir Shalem, Eric Tran, Robert Eil, Madhusudhanan Sukumar, Eva Perez Guijarro, Chi-Ping Day, Paul Robbins, Steve Feldman, Glenn Merlino, Feng Zhang, Nicholas P Restifo
Somatic gene mutations can alter the vulnerability of cancer cells to T-cell-based immunotherapies. Here we perturbed genes in human melanoma cells to mimic loss-of-function mutations involved in resistance to these therapies, by using a genome-scale CRISPR-Cas9 library that consisted of around 123,000 single-guide RNAs, and profiled genes whose loss in tumour cells impaired the effector function of CD8(+) T cells. The genes that were most enriched in the screen have key roles in antigen presentation and interferon-γ signalling, and correlate with cytolytic activity in patient tumours from The Cancer Genome Atlas...
August 7, 2017: Nature
https://www.readbyqxmd.com/read/28783166/anti-leukemic-activity-of-microrna-26a-in-a-chronic-lymphocytic-leukemia-mouse-model
#15
L D'Abundo, E Callegari, A Bresin, A Chillemi, B K Elamin, P Guerriero, X Huang, E Saccenti, E M A A Hussein, F Casciano, P Secchiero, G Zauli, G A Calin, G Russo, L J Lee, C M Croce, G Marcucci, S Sabbioni, F Malavasi, M Negrini
Dysregulation of microRNAs (miRNAs) plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL). The Eμ-TCL1 transgenic mouse develops a form of leukemia that is similar to the aggressive type of human B-CLL, and this valuable model has been widely used for testing novel therapeutic approaches. Here, we adopted this model to investigate the potential effects of miR-26a, miR-130an and antimiR-155 in CLL therapy. Improved delivery of miRNA molecules into CLL cells was obtained by developing a novel system based on lipid nanoparticles conjugated with an anti-CD38 monoclonal antibody...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28782211/bisphosphonate-guidelines-for-treatment-and-prevention-of-myeloma-bone-disease
#16
Oi Lin Lee, Noemi Horvath, Cindy Lee, Doug Joshua, Joy Ho, Jeff Szer, Hang Quach, Andrew Spencer, Simon Harrison, Peter Mollee, Andrew W Roberts, Dipti Talaulikar, Ross Brown, Bradley Augustson, Silvia Ling, Wilfrid Jaksic, John Gibson, Anna Kalff, Anna Johnston, Akash Kalro, Chris Ward, H Miles Prince, Andrew Zannettino
Multiple myeloma (MM) is a haematological malignancy characterised by the clonal proliferation of plasma cells in the bone marrow. More than 80% of patients with MM display evidence of myeloma bone disease (MBD), characterised by the formation of osteolytic lesions throughout the axial and appendicular skeleton. MBD significantly increases the risk of skeletal-related events such as pathologic fracture, spinal cord compression and hypercalcaemia. MBD is the result of MM plasma cells-mediated activation of osteoclast activity and suppression of osteoblast activity...
August 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28781967/immunotherapeutic-strategies-for-gastric-carcinoma-a-review-of-preclinical-and-clinical-recent-development
#17
REVIEW
Mohamed Abozeid, Antonio Rosato, Roberta Sommaggio
Gastric carcinoma (GC) is the 2nd most common cause of cancer-related death. Despite advances in conventional treatment and surgical interventions, a high percentage of GC patients still have poor survival. Recently, immunotherapy has become a promising approach to treat GC. Here, we present preclinical and clinical studies encouraging the use of vaccination, adoptive T-cell therapy (ACT), and immune checkpoint inhibitors, such as programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28778019/photoinactivation-of-multidrug-resistant-bacteria-by-monomeric-methylene-blue-conjugated-gold-nanoparticles
#18
Shakir Khan, Shahper N Khan, Ramovatar Meena, Ayaz M Dar, Ruchita Pal, Asad U Khan
Multidrug resistant (MDR) bacterial infections have become a severe threat to the community health due to a progressive rise in antibiotic resistance. Nanoparticle-based photodynamic therapy (PDT) is increasingly been adopted as a potential antimicrobial option, yet the cytotoxicity associated with PDT is quite unspecific. Herein, we show Concanavalin-A (ConA) directed dextran capped gold nanoparticles (GNPDEX-ConA) enhanced the efficacy and selectivity of methylene blue (MB) induced killing of multidrug resistant clinical isolates...
July 24, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28777538/microinjection-for-the-ex-vivo-modification-of-cells-with-artificial-organelles
#19
Peter Tiefenboeck, Jong Ah Kim, Ferdinand Trunk, Tamara Eicher, Erica Russo, Alvaro Teijeira, Cornelia Halin, Jean-Christophe Leroux
Microinjection is extensively used across fields to deliver material intracellularly. Here we address the fundamental aspects of introducing exogenous organelles into cells to endow them with artificial functions. Nanocarriers encapsulating biologically active cargo or extreme intraluminal pH were injected directly into the cytosol of cells, where they bypassed subcellular processing pathways and persisted intact for several days. Nanocarriers' size was found to dictate their intracellular distribution pattern upon injection, with larger vesicles adopting polarized agglomerated distributions and smaller colloids spreading evenly in the cytosol...
August 4, 2017: ACS Nano
https://www.readbyqxmd.com/read/28771456/notes-from-the-field-preliminary-results-after-implementation-of-a-universal-treatment-program-test-and-start-for-persons-living-with-hiv-infection-lesotho-october-2015-february-2017
#20
Amee M Schwitters
Lesotho, a small, mountainous country completely surrounded by the Republic of South Africa, has a population of approximately 2 million persons with an estimated gross national income of $1,280 per capita; 73% of the population resides in rural areas (1). Lesotho has a generalized human immunodeficiency virus (HIV) epidemic (2). In 2014, the prevalence of HIV infection among persons aged 15-49 years was 24.6%, with an incidence of 1.9 new infections per 100 person-years of exposure (3). As the leading cause of premature death, HIV/AIDS (acquired immunodeficiency syndrome) has contributed to Lesotho's reporting the shortest life expectancy at birth among 195 countries and territories (4)...
August 4, 2017: MMWR. Morbidity and Mortality Weekly Report
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