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Immune engineering

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https://www.readbyqxmd.com/read/29473469/immunotherapy-for-thoracic-oncology-gone-viral
#1
Manish R Patel
Immune therapy has now been incorporated into the standard of care for non-small-cell lung cancer based on randomized trials showing superiority of anti-PD1 antibodies compared with chemotherapy. Thus there is a renewed interest in immune approaches to treating lung cancer. One promising approach is with oncolytic viruses that either naturally or through engineering, preferentially infect or kill cancer cells. In preclinical models of different thoracic cancers, it has been found that these viruses can induce immune responses through multiple mechanisms...
April 2018: Immunotherapy
https://www.readbyqxmd.com/read/29472120/targeting-cd6-for-the-treatment-of-experimental-autoimmune-uveitis
#2
Lingjun Zhang, Yan Li, Wen Qiu, Brent A Bell, Nina Dvorina, William M Baldwin, Nora Singer, Timothy Kern, Rachel R Caspi, David A Fox, Feng Lin
OBJECTIVE: CD6 is emerging as a new target for treating many pathological conditions in which T cells are integrally involved, but even the latest data from studies of CD6 gene engineered mice were still contradictory. To address this issue, we studied experimental autoimmune uveitis (EAU), a model of autoimmune uveitis, in wild-type (WT) and CD6 knockout (KO) mice. METHODS: After EAU induction in WT and CD6 KO mice, we evaluated ocular inflammation and compared retinal antigen-specific T-cell responses using scanning laser ophthalmoscopy, spectral-domain optical coherence tomography, histopathology, and T cell recall assays...
February 19, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29471699/atezolizumab-for-the-treatment-of-colorectal-cancer-the-latest-evidence-and-clinical-potential
#3
Gonzalo Tapia Rico, Timothy J Price
Atezolizumab is a fully humanized, engineered monoclonal antibody (MAb) of IgG1 isotype that specifically targets programmed death ligand 1 (PD-L1), a key molecule in the cancer-immunity pathway. Atezolizumab is currently approved for the treatment of metastatic non-small-cell lung cancer (NSCLC) and advanced urothelial carcinomas. Areas covered: In this review, we will present the available (early phase clinical trials) data supporting the efficacy of atezolizumab for the treatment of metastatic colorectal cancer (mCRC)...
February 23, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29467958/pharmacokinetic-properties-of-radiolabeled-mutant-interleukin-2v-a-pet-imaging-study
#4
Siddesh V Hartimath, Valeria Manuelli, Rolf Zijlma, Alberto Signore, Tapan K Nayak, Anne Freimoser-Grundschober, Christian Klein, Rudi A J O Dierckx, Erik F J de Vries
Interleukin-2 (IL2) is a cytokine that can stimulate cytotoxic immune cells to attack infected and malignant cells. Unfortunately, IL2 can also cause serious immune-related toxicity. Recently, a mutant of IL2 (IL2v) with abolished CD25 binding, increased plasma half-life and less toxicity was engineered. Unlike wild-type IL2 (wt-IL2), mutant IL2v does not bind to the α-subunit (CD25) of the high affinity IL2αβγ receptor, but only to its β and γ subunit. Here, we investigated the biological properties of IL2v and compared with the wt-IL2 using fluorine-18 and PET...
January 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29467769/cd137-cd154-expression-as-a-regulatory-t-cell-treg-specific-activation-signature-for-identification-and-sorting-of-stable-human-tregs-from-in-vitro-expansion-cultures
#5
Anna Nowak, Dominik Lock, Petra Bacher, Thordis Hohnstein, Katrin Vogt, Judith Gottfreund, Pascal Giehr, Julia K Polansky, Birgit Sawitzki, Andrew Kaiser, Jörn Walter, Alexander Scheffold
Regulatory T cells (Tregs) are an attractive therapeutic tool for several different immune pathologies. Therapeutic Treg application often requires prolonged in vitro culture to generate sufficient Treg numbers or to optimize their functionality, e.g., via genetic engineering of their antigen receptors. However, purity of clinical Treg expansion cultures is highly variable, and currently, it is impossible to identify and separate stable Tregs from contaminating effector T cells, either ex vivo or after prior expansion...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29467314/a-prominent-role-of-the-human-cytomegalovirus-ul8-glycoprotein-restraining-pro-inflammatory-cytokine-production-by-myeloid-cells-at-late-times-during-infection
#6
Natàlia Pérez-Carmona, Pablo Martínez-Vicente, Domènec Farré, Ildar Gabaev, Martin Messerle, Pablo Engel, Ana Angulo
Human cytomegalovirus (HCMV) persistence in infected individuals relies on a plethora of mechanisms to efficiently reduce host immune responses. To that end, HCMV commits a variety of gene products, some of which have not been identified yet. Here we characterized the UL8 gene, which consists of two exons, sharing the first with the HCMV RL11 family member UL7 UL8 is a transmembrane protein with an N-terminal immunoglobulin (Ig)-like domain in common with UL7 but with an extended stalk and a distinctive cytoplasmic tail...
February 21, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29467299/in-situ-formed-reactive-oxygen-species-responsive-scaffold-with-gemcitabine-and-checkpoint-inhibitor-for-combination-therapy
#7
Chao Wang, Jinqiang Wang, Xudong Zhang, Shuangjiang Yu, Di Wen, Quanyin Hu, Yanqi Ye, Hunter Bomba, Xiuli Hu, Zhuang Liu, Gianpietro Dotti, Zhen Gu
Patients with low-immunogenic tumors respond poorly to immune checkpoint blockade (ICB) targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway. Conversely, patients responding to ICB can experience various side effects. We have thus engineered a therapeutic scaffold that, when formed in situ, allows the local release of gemcitabine (GEM) and an anti-PD-L1 blocking antibody (aPDL1) with distinct release kinetics. The scaffold consists of reactive oxygen species (ROS)-degradable hydrogel that releases therapeutics in a programmed manner within the tumor microenvironment (TME), which contains abundant ROS...
February 21, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29462900/next-generation-immunotherapy-for-pancreatic-cancer-dna-vaccination-is-seeking-new-combo-partners
#8
REVIEW
Paola Cappello, Claudia Curcio, Giorgia Mandili, Cecilia Roux, Sara Bulfamante, Francesco Novelli
Pancreatic Ductal Adenocarcinoma (PDA) is an almost incurable radio- and chemo-resistant tumor, and its microenvironment is characterized by a strong desmoplastic reaction associated with a significant infiltration of T regulatory lymphocytes and myeloid-derived suppressor cells (Tregs, MDSC). Investigating immunological targets has identified a number of metabolic and cytoskeletal related molecules, which are typically recognized by circulating antibodies. Among these molecules we have investigated alpha-enolase (ENO1), a glycolytic enzyme that also acts a plasminogen receptor...
February 16, 2018: Cancers
https://www.readbyqxmd.com/read/29462157/a-mouse-model-study-of-toxicity-and-biodistribution-of-a-replication-defective-adenovirus-serotype-5-virus-with-its-genome-engineered-to-contain-a-decoy-hyper-binding-site-to-sequester-and-suppress-oncogenic-hmga1-as-a-new-cancer-treatment-therapy
#9
Faizule Hassan, Sarah L Lossie, Ellen P Kasik, Audrey M Channon, Shuisong Ni, Michael A Kennedy
The HGMA1 architectural transcription factor is highly overexpressed in many human cancers. Because HMGA1 is a hub for regulation of many oncogenes, its overexpression in cancer plays a central role in cancer progression and therefore HMGA1 is gaining increasing attention as a target for development of therapeutic approaches to suppress either its expression or action in cancer cells. We have developed the strategy of introducing decoy hyper binding sites for HMGA1 into the nucleus of cancer cells with the goal of competetively sequestering overexpressed HMGA1 and thus suppressing its oncogenic action...
2018: PloS One
https://www.readbyqxmd.com/read/29459870/is-the-a-chain-the-engine-that-drives-the-diversity-of-c1q-functions-revisiting-its-unique-structure
#10
Berhane Ghebrehiwet, Evelyn Kandov, Uday Kishore, Ellinor I B Peerschke
The immunopathological functions associated with human C1q are still growing in terms of novelty, diversity, and pathologic relevance. It is, therefore, not surprising that C1q is being recognized as an important molecular bridge between innate and adaptive immunity. The secret of this functional diversity, in turn, resides in the elegant but complex structure of the C1q molecule, which is assembled from three distinct gene products: A, B, and C, each of which has evolved from a separate and unique ancestral gene template...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29459867/the-multirole-of-liposomes-in-therapy-and-prevention-of-infectious-diseases
#11
REVIEW
Roberto Nisini, Noemi Poerio, Sabrina Mariotti, Federica De Santis, Maurizio Fraziano
Liposomes are closed bilayer structures spontaneously formed by hydrated phospholipids that are widely used as efficient delivery systems for drugs or antigens, due to their capability to encapsulate bioactive hydrophilic, amphipathic, and lipophilic molecules into inner water phase or within lipid leaflets. The efficacy of liposomes as drug or antigen carriers has been improved in the last years to ameliorate pharmacokinetics and capacity to release their cargo in selected target organs or cells. Moreover, different formulations and variations in liposome composition have been often proposed to include immunostimulatory molecules, ligands for specific receptors, or stimuli responsive compounds...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29459866/current-status-of-gene-engineering-cell-therapeutics
#12
REVIEW
Aurore Saudemont, Laurent Jespers, Timothy Clay
Ex vivo manipulations of autologous patient's cells or gene-engineered cell therapeutics have allowed the development of cell and gene therapy approaches to treat otherwise incurable diseases. These modalities of personalized medicine have already shown great promises including product commercialization for some rare diseases. The transfer of a chimeric antigen receptor or T cell receptor genes into autologous T cells has led to very promising outcomes for some cancers, and particularly for hematological malignancies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29459859/next-generation-vaccines-based-on-bacille-calmette-gu%C3%A3-rin
#13
REVIEW
Natalie E Nieuwenhuizen, Stefan H E Kaufmann
Tuberculosis (TB), caused by the intracellular bacterium Mycobacterium tuberculosis (Mtb), remains a major health threat. A live, attenuated mycobacterium known as Bacille Calmette-Guérin (BCG), derived from the causative agent of cattle TB, Mycobacterium bovis , has been in clinical use as a vaccine for 90 years. The current incidence of TB demonstrates that BCG fails to protect sufficiently against pulmonary TB, the major disease manifestation and source of dissemination. The protective efficacy of BCG is on average 50% but varies substantially with geographical location and is poorer in those with previous exposure to mycobacteria...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29456740/an-obligatory-anaerobic-salmonella-typhimurium-strain-redirects-m2-macrophages-to-the-m1-phenotype
#14
Mei Yang, Juan Xu, Qi Wang, An-Qin Zhang, Kun Wang
A genetically engineered Salmonella typhimurium strain that may be applied in the medically useful therapeutic strategy of using bacterial agents to target breast cancer in a tumor-bearing nude mouse model has been previously reported. Furthermore, immune cell accumulation in breast tumor types has been observed, particularly distributed in regions surrounding the bacteria. M2 macrophages are associated with breast cancer aggressiveness, whereas M1 macrophages are prone to devouring bacteria and killing cancer cells...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29453386/anti-fibrotic-effects-of-cxcr4-targeting-i-body-ad-114-in-preclinical-models-of-pulmonary-fibrosis
#15
K Griffiths, D M Habiel, J Jaffar, U Binder, W G Darby, C G Hosking, A Skerra, G P Westall, C M Hogaboam, M Foley
Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease that is prevalent in individuals >50 years of age, with a median survival of 3-5 years and limited therapeutic options. The disease is characterized by collagen deposition and remodeling of the lung parenchyma in a process that is thought to be driven by collagen-expressing immune and structural cells. The G-protein coupled C-X-C chemokine receptor 4, CXCR4, is a candidate therapeutic target for IPF owing to its role in the recruitment of CXCR4 + fibrocytes from the bone marrow to fibrotic lung tissue and its increased expression levels by structural cells in fibrotic lung tissue...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453266/the-gills-of-reef-fish-support-a-distinct-microbiome-influenced-by-host-specific-factors
#16
Zoe A Pratte, Marc Besson, Rebecca D Hollman, Frank J Stewart
Teleost fish represent the most diverse of the vertebrate groups and play important roles in food webs, as ecosystem engineers, and as vectors for microorganisms. However, the microbial ecology of fishes remains underexplored for most host taxa, and for certain niches on the fish body. This is particularly true for the gills, the key sites for respiration and waste exchange in fishes. Here, we provide a comprehensive analysis of the gill microbiome. We focus on ecologically diverse taxa from coral reefs around Moorea, sampling the gill and intestines of adults and juveniles representing 15 families...
February 16, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29450416/a-g-quadruplex-motif-at-the-3-end-of-sgrnas-improves-crispr-cas9-based-genome-editing-efficiency
#17
Smita Nahar, Paras Sehgal, Mohd Azhar, Manish Rai, Amrita Singh, Sridhar Sivasubbu, Debojyoti Chakraborty, Souvik Maiti
Originating as a component of prokaryotic adaptive immunity, the type II CRISPR/Cas9 system has been repurposed for targeted genome editing in various organisms. Although Cas9 can bind and cleave DNA efficiently under in vitro conditions, its activity inside a cell can vary dramatically between targets owing to the differences between genomic loci and the availability of enough Cas9/sgRNA (single guide RNA) complex molecules for cleavage. Most methods have so far relied on Cas9 protein engineering or base modifications in the sgRNA sequence to improve CRISPR/Cas9 activity...
February 16, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29448937/engineering-chimeric-antigen-receptor-t-cells-for-cancer-treatment
#18
REVIEW
Baixin Ye, Creed M Stary, Xuejun Li, Qingping Gao, Chunsheng Kang, Xiaoxing Xiong
Intratumor heterogeneity of tumor clones and an immunosuppressive microenvironment in cancer ecosystems contribute to inherent difficulties for tumor treatment. Recently, chimeric antigen receptor (CAR) T-cell therapy has been successfully applied in the treatment of B-cell malignancies, underscoring its great potential in antitumor therapy. However, functional challenges of CAR-T cell therapy, especially in solid tumors, remain. Here, we describe cancer-immunity phenotypes from a clonal-stromal-immune perspective and elucidate mechanisms of T-cell exhaustion that contribute to tumor immune evasion...
February 15, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29446741/whats%C3%A2-new-in-gene-therapy-of-hemophilia
#19
E Carlos Rodriguez-Merchan
BACKGROUND: Several methods have been investigated to effectively and safely transmit genes that stimulate cells to release therapeutic factor VIII (FVIII) and factor IX (FIX) into the circulation of people with hemophilia (PWH). OBJECTIVE: To review the role of gene therapy (GT) in PWH. METHODS: A Cochrane Library and PubMed (MEDLINE) search related to the role of GT in hemophilia was analyzed. RESULTS: The most promising vectors for hemophilia GT are adeno-associated virus (AAV) and lentivirus...
February 14, 2018: Current Gene Therapy
https://www.readbyqxmd.com/read/29446615/leveraging-engineering-of-cells-for-drug-delivery
#20
Zhaowei Chen, Quanyin Hu, Zhen Gu
Cell therapy has become a momentum-gathering treatment strategy for a variety of diseases, including cancer, diabetes, hemophilia, and cardiomyopathy. However, clinical applications of conventional cell therapies have often been compromised by rapid decline in viability and function of the transplanted cells due to host recognition and subsequent foreign body rejection. Along this line, cell engineering technologies such as cell encapsulation within microcapsules and immobilization in porous scaffolds have been implemented to address the immunosuppression concerns...
February 15, 2018: Accounts of Chemical Research
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