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Engineered immune cells

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https://www.readbyqxmd.com/read/28820071/antibody-fragments-as-potential-biopharmaceuticals-for-cancer-therapy-success-and-limitations
#1
Roman V Kholodenko, Daniel V Kalinovsky, Igor I Doronin, Eugene D Ponomarev, Irina V Kholodenko
Monoclonal antibodies (mAbs) are an important class of therapeutic agents approved for the therapy of many types of malignancies. However, in certain cases applications of conventional mAbs have several limitations in anticancer immunotherapy. These limitations include insufficient efficacy and adverse effects. The antigen-binding fragments of antibodies have a considerable potential to overcome the disadvantages of conventional mAbs, such as poor penetration into solid tumors and Fc-mediated bystander activation of the immune system...
August 17, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28818634/mining-na%C3%A3-ve-rabbit-antibody-repertoires-by-phage-display-for-monoclonal-antibodies-of-therapeutic-utility
#2
Haiyong Peng, Thomas Nerreter, Jing Chang, Junpeng Qi, Xiuling Li, Pabalu Karunadharma, Gustavo Martinez, Mohammad Fallahi, Jo Soden, Jim Freeth, Roger R Beerli, Ulf Grawunder, Michael Hudecek, Christoph Rader
Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but in some cases also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large naïve rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies in chimeric rabbit/human Fab format and validated it by next-generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity...
August 14, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28816564/cytotoxicity-screening-and-cytokine-profiling-of-nineteen-nanomaterials-enables-hazard-ranking-and-grouping-based-on-inflammogenic-potential
#3
Kunal Bhattacharya, Gözde Kiliç, Pedro M Costa, Bengt Fadeel
Engineered nanomaterials (ENMs) are being produced for an increasing number of applications. Therefore, it is important to assess and categorize ENMs on the basis of their hazard potential. The immune system is the foremost defence against foreign bodies. Here we performed cytokine profiling of a panel of nineteen representative ENMs procured from the Joint Research Centre (JRC) and commercial sources. Physicochemical characterization was performed using dynamic light scattering. The ENMs were all shown to be endotoxin content free...
August 17, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28816104/the-immune-response-to-allogeneic-differentiated-mesenchymal-stem-cells-in-the-context-of-bone-tissue-engineering
#4
Caoimhe H Kiernan, Eppo B Wolvius, Pieter A J Brama, Eric Farrell
The use of allogeneic differentiated mesenchymal stem cells (MSCs) to mediate bone formation may be a potential alternative to the current gold standards of bone repair. While it is known that undifferentiated MSCs are immunomodulatory and weakly immunogenic, the host immune reaction to differentiated MSCs is less known. Implantation of allogeneic osteogenic or chondrogenically differentiated MSC pellets may be promising routes to induce bone repair via the processes of intramembranous and endochondral ossification...
August 17, 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/28811974/ex-vivo-assessment-of-drug-response-on-breast-cancer-primary-tissue-with-preserved-microenvironments
#5
Manuele G Muraro, Simone Muenst, Valentina Mele, Luca Quagliata, Giandomenica Iezzi, Alexandar Tzankov, Walter P Weber, Giulio C Spagnoli, Savas D Soysal
Interaction between cancerous, non-transformed cells, and non-cellular components within the tumor microenvironment plays a key role in response to treatment. However, short-term culture or xenotransplantation of cancer specimens in immunodeficient animals results in dramatic modifications of the tumor microenvironment, thus preventing reliable assessment of compounds or biologicals of potential therapeutic relevance. We used a perfusion-based bioreactor developed for tissue engineering purposes to successfully maintain the tumor microenvironment of freshly excised breast cancer tissue obtained from 27 breast cancer patients and used this platform to test the therapeutic effect of antiestrogens as well as checkpoint-inhibitors on the cancer cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28806522/development-of-a-recombinant-multifunctional-biomacromolecule-for-targeted-gene-transfer-to-prostate-cancer-cells
#6
Arash Hatefi, Zahra Karjoo, Alireza Nomani
The objective of this study was to genetically engineer a fully functional single chain fusion peptide composed of motifs from diverse biological and synthetic origins that can perform multiple tasks including DNA condensation, cell targeting, cell transfection, particle shielding from immune system and effective gene transfer to prostate tumors. To achieve the objective, a single chain biomacromolecule (vector) consisted of four repetative units of histone H2A peptide, fusogenic peptide GALA, short elastin-like peptide and PC-3 cell targeting peptide was designed...
August 14, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28806273/the-changing-landscape-of-gene-editing-in-hematopoietic-stem-cells-a-step-towards-cas9-clinical-translation
#7
Daniel P Dever, Matthew H Porteus
PURPOSE OF REVIEW: Since the discovery two decades ago that programmable endonucleases can be engineered to modify human cells at single nucleotide resolution, the concept of genome editing was born. Now these technologies are being applied to therapeutically relevant cell types, including hematopoietic stem cells (HSC), which possess the power to repopulate an entire blood and immune system. The purpose of this review is to discuss the changing landscape of genome editing in hematopoietic stem cells (GE-HSC) from the discovery stage to the preclinical stage, with the imminent goal of clinical translation for the treatment of serious genetic diseases of the blood and immune system...
August 12, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28804866/virally-vectored-vaccine-delivery-medical-needs-mechanisms-advantages-and-challenges
#8
Daniel D Pinschewer
Vaccines represent one of the most successful chapters in the history of medicine. Over the past decades, the advent of recombinant cDNA technology has enabled the biomedical community to genetically engineer viruses for vaccine delivery purposes. As a starting point, this review evaluates the unmet medical needs, which drive scientists and industry to exploit such fundamentally new technology for human vaccination. The author discusses the molecular functioning, production and safety profile of replication-competent and -deficient viral vector systems, representing two fundamentally distinct classes of "genetic vaccines"...
August 14, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28796529/designed-ankyrin-repeat-proteins-as-her2-targeting-domains-in-chimeric-antigen-receptor-engineered-t-cells
#9
Elizabeth Siegler, Si Li, Yu Jeong Kim, Pin Wang
Chimeric antigen receptor (CAR) engineering is a branch of cancer immunotherapy that equips immune cells to target tumor antigens expressed on the cell surface using antibody-derived single-chain variable fragments (scFvs). However, other antibody mimetics, such as designed ankyrin repeat proteins (DARPins), can also serve as antigen-binding domains in CARs. This study shows that CAR-engineered T (CAR-T) cells utilizing Her2-targeting DARPins G3 and 929 can target human epidermal growth factor receptor 2 (Her2)-overexpressing cancer cells as effectively as CAR-T cells with the scFv 4D5 in vitro, and G3 CAR-T cells can slow or eliminate tumor growth in vivo as effectively as 4D5 CAR-T cells...
June 22, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28796297/transfer-of-tomato-immune-receptor-ve1-confers-ave1-dependent-verticillium-resistance-in-tobacco-and-cotton
#10
Yin Song, Linlin Liu, Yidong Wang, Dirk-Jan Valkenburg, Xianlong Zhang, Longfu Zhu, Bart P H J Thomma
Verticillium wilts caused by soil-borne fungal species of the Verticillium genus are economically important plant diseases that affect a wide range of host plants, and are notoriously difficult to combat. Perception of pathogen(-induced) ligands by plant immune receptors is a key component of plant innate immunity. In tomato, race-specific resistance to Verticillium wilt is governed by the cell surface-localized immune receptor Ve1 through recognition of the effector protein Ave1 that is secreted by race 1 strains of Verticillium spp...
August 10, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28793786/hemophilia-gene-therapy-ready-for-prime-time
#11
Thierry VandenDriessche, Marinee K L Chuah
Hemophilia A and B are congenital X-linked bleeding disorders caused by mutations in the genes encoding for the blood clotting factor VIII (FVIII) or factor IX (FIX), respectively. Since the beginning of gene therapy, hemophilia has been considered an attractive disease target that served as a trailblazer for the field at large. Different technologies have been explored to efficiently and safely deliver the therapeutic FVIII and FIX genes into the patients' cells. Currently, the most promising vectors for hemophilia gene therapy are adeno-associated viral vectors (AAV) and lentiviral vectors...
August 10, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28782184/integrin-mediated-interactions-control-macrophage-polarization-in-3d-hydrogels
#12
Byung-Hyun Cha, Su Ryon Shin, Jeroen Leijten, Yi-Chen Li, Sonali Singh, Julie C Liu, Nasim Annabi, Reza Abdi, Mehmet R Dokmeci, Nihal Engin Vrana, Amir M Ghaemmaghami, Ali Khademhosseini
Adverse immune reactions prevent clinical translation of numerous implantable devices and materials. Although inflammation is an essential part of tissue regeneration, chronic inflammation ultimately leads to implant failure. In particular, macrophage polarity steers the microenvironment toward inflammation or wound healing via the induction of M1 and M2 macrophages, respectively. Here, this paper demonstrates that macrophage polarity within biomaterials can be controlled through integrin-mediated interactions between human monocytic THP-1 cells and collagen-derived matrix...
August 7, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28780888/anti-gd2-immunotherapy-for-neuroblastomas
#13
Sameer Sait, Shakeel I Modak
Current therapeutic approaches for high-risk neuroblastoma (HR-NB) include high-dose chemotherapy, surgery and radiotherapy; interventions that are associated with long and short-term toxicities. Effective immunotherapy holds particular promise for improving survival and quality of life by reducing exposure to cytotoxic agents. GD2, a surface glycolipid is the most common target for immunotherapy. Areas covered: We review the status of anti-GD2 immunotherapies currently in clinical use for neuroblastomas and novel GD2-targeted strategies in preclinical development...
August 7, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28780115/foreign-gene-expression-and-induction-of-antibody-response-by-recombinant-fowl-adenovirus-9-based-vectors-with-exogenous-promoters
#14
James G Ackford, Juan C Corredor, Yanlong Pei, Peter J Krell, Grégoy Bédécarrats, E Va Nagy
Fowl adenoviruses (FAdVs) are promising vectors for poultry vaccines and gene therapy. The commonly used human cytomegalovirus (CMV) promoter in recombinant FAdV-9 viruses (recFAdV-9s) leads to foreign gene expression that elicits an antibody response. Despite its strength, studies have shown that the CMV promoter is prone to silencing by methylation hampering the in vivo application of vectors containing this promoter. Therefore, to improve our virus vector system and circumvent potential limitations of silencing, we engineered recFAdV-9s with foreign gene expression cassettes carrying the CMV enhancer/chicken β-actin (CAG) or the human elongation factor 1 alpha (EF1α) promoters with or without the posttranscriptional regulatory element of woodchuck hepatitis virus (WPRE)...
August 2, 2017: Vaccine
https://www.readbyqxmd.com/read/28771849/in-vivo-evaluation-of-an-engineered-cyclotide-as-specific-cxcr4-imaging-reagent
#15
Wojciech G Lesniak, Teshome Aboye, Samit Chatterjee, Julio A Camarero, Sridhar Nimmagadda
The CXCR4 chemokine receptor plays a key regulatory role in many biological functions, including embryonic development and controlling leukocyte functions during inflammation and immunity. CXCR4 has been also associated with multiple types of cancers where its overexpression/activation promotes metastasis, angiogenesis, and tumor growth and/or survival. Furthermore, CXCR4 is involved in HIV replication, as it is a co-receptor for viral entry into host cells. Altogether, these features make CXCR4 a very attractive target for the development of imaging and therapeutic agents...
August 3, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28771731/repairing-the-vibratory-vocal-fold
#16
Jennifer L Long
OBJECTIVE: A vibratory vocal fold replacement would introduce a new treatment paradigm for structural vocal fold diseases such as scarring and lamina propria loss. This work implants a tissue-engineered replacement for vocal fold lamina propria and epithelium in rabbits and compares histology and function to injured controls and orthotopic transplants. Hypotheses were that the cell-based implant would engraft and control the wound response, reducing fibrosis and restoring vibration. STUDY DESIGN: Translational research...
August 3, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28771620/a-benign-helminth-alters-the-host-immune-system-and-the-gut-microbiota-in-a-rat-model-system
#17
Laura Wegener Parfrey, Milan Jirků, Radek Šíma, Marie Jalovecká, Bohumil Sak, Karina Grigore, Kateřina Jirků Pomajbíková
Helminths and bacteria are major players in the mammalian gut ecosystem and each influences the host immune system and health. Declines in helminth prevalence and bacterial diversity appear to play a role in the dramatic rise of immune mediated inflammatory diseases (IMIDs) in western populations. Helminths are potent modulators of immune system and their reintroduction is a promising therapeutic avenue for IMIDs. However, the introduction of helminths represents a disturbance for the host and it is important to understand the impact of helminth reintroduction on the host, including the immune system and gut microbiome...
2017: PloS One
https://www.readbyqxmd.com/read/28770166/genomic-signature-of-the-natural-oncolytic-herpes-simplex-virus-hf10-and-its-therapeutic-role-in-preclinical-and-clinical-trials
#18
REVIEW
Ibrahim Ragab Eissa, Yoshinori Naoe, Itzel Bustos-Villalobos, Toru Ichinose, Maki Tanaka, Wu Zhiwen, Nobuaki Mukoyama, Taishi Morimoto, Noriyuki Miyajima, Hasegawa Hitoki, Seiji Sumigama, Branko Aleksic, Yasuhiro Kodera, Hideki Kasuya
Oncolytic viruses (OVs) are opening new possibilities in cancer therapy with their unique mechanism of selective replication within tumor cells and triggering of antitumor immune responses. HF10 is an oncolytic herpes simplex virus-1 with a unique genomic structure that has non-engineered deletions and insertions accompanied by frame-shift mutations, in contrast to the majority of engineered OVs. At the genetic level, HF10 naturally lacks the expression of UL43, UL49.5, UL55, UL56, and latency-associated transcripts, and overexpresses UL53 and UL54...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28767707/murine-gammaherpesvirus-m2-antigen-modulates-splenic-b-cell-activation-and-terminal-differentiation-in-vivo
#19
Shariya Terrell, Samuel H Speck
Murine gammaherpesvirus 68 (MHV68) infection of laboratory strains of mice has provided a tractable small animal model for dissecting gammaherpesvirus pathogenesis. The MHV68 latency associated antigen M2 promotes viral latency establishment in germinal center (GC) B cells and plays an important role in virus infection of plasma cells (PCs), which is linked to virus reactivation. More recently, M2 has been highlighted as a potent immunomodulatory molecule capable of hindering both cell-mediated and humoral immunity to MHV68 infection and subsequent challenges...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28767408/integration-of-genomic-transcriptomic-and-functional-profiles-of-aggressive-osteosarcomas-across-multiple-species
#20
Lara E Davis, Sophia Jeng, Matthew N Svalina, Elaine Huang, Janét Pittsenbarger, Emma L Cantor, Noah Berlow, Bernard Seguin, Atiya Mansoor, Shannon K McWeeney, Charles Keller
In complex, highly unstable genomes such as in osteosarcoma, targeting aberrant checkpoint processes (metabolic, cell cycle or immune) may prove more successful than targeting specific kinase or growth factor signaling pathways. Here, we establish a comparative oncology approach characterizing the most lethal osteosarcomas identified in a biorepository of tumors from three different species: human, mouse and canine. We describe the development of a genetically-engineered mouse model of osteosarcoma, establishment of primary cell cultures from fatal human tumors, and a biorepository of osteosarcoma surgical specimens from pet dogs...
July 25, 2017: Oncotarget
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