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Immune engineering

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https://www.readbyqxmd.com/read/29035749/chemical-remodeling-cell-surface-glycans-for-immunotargeting-of-tumor-cells
#1
Xuexia Li, Xiaoyan Xu, Xiongjian Rao, Yinping Tian, Wen Yi
Recruitment of human endogenous antibodies to target and eliminate tumor cells is a promising therapeutic strategy in the biomedical field. Current antibody-recruiting molecules are typically bi-functional agents that utilize cell-surface receptor binding property for targeting. This approach has intrinsic limitations due to the heterogeneity of tumor cells and the limited number of receptors on the cell surface. Here we report a targeting strategy based on remodeling of cell surface glycans through metabolic engineering and bioorthogonal chemical ligation...
October 10, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/29034637/-development-identification-and-application-of-33-monoclonal-antibodies-against-cardiac-troponin-t
#2
Yuehong Hu, Zimin Chen, Yuxiang Chen, Yinghui Yang, Shuying Wei, Liuwei Song, Guoliang Zhou, Shengxiang Ge
The aim of this study is to prepare and characterize cardiac troponin T (cTnT) monoclonal antibodies (mAb), and further develop a chemiluminescence quantitative detection assay for cTnT. BALB/c mice were immunized with recombinant cTnT antigen, and specific mAbs were prepared using conventional hybridoma technique and screened by indirect ELISA method. To identify the epitopes, several cTnT peptide fragments were synthesized or expressed by genetic engineering. A double antibody sandwich ELISA method was used to screen the mAb pairs for cTnT detection, and the automatic chemiluminescence detection assay for cTnT was developed...
December 25, 2016: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/29033339/transmissible-viral-vaccines
#3
REVIEW
James J Bull, Mark W Smithson, Scott L Nuismer
Genetic engineering now enables the design of live viral vaccines that are potentially transmissible. Some designs merely modify a single viral genome to improve on the age-old method of attenuation whereas other designs create chimeras of viral genomes. Transmission has the benefit of increasing herd immunity above that achieved by direct vaccination alone but also increases the opportunity for vaccine evolution, which typically undermines vaccine utility. Different designs have different epidemiological consequences but also experience different evolution...
October 12, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/29031786/differentiation-and-protective-capacity-of-virus-specific-cd8-t-cells-suggest-murine-norovirus-persistence-in-an-immune-privileged-enteric-niche
#4
Vesselin T Tomov, Olesya Palko, Chi Wai Lau, Ajinkya Pattekar, Yuhang Sun, Ralitza Tacheva, Bertram Bengsch, Sasikanth Manne, Gabriela L Cosma, Laurence C Eisenlohr, Timothy J Nice, Herbert W Virgin, E John Wherry
Noroviruses can establish chronic infections with active viral shedding in healthy humans but whether persistence is associated with adaptive immune dysfunction is unknown. We used genetically engineered strains of mouse norovirus (MNV) to investigate CD8(+) T cell differentiation during chronic infection. We found that chronic infection drove MNV-specific tissue-resident memory (Trm) CD8(+) T cells to a differentiation state resembling inflationary effector responses against latent cytomegalovirus with only limited evidence of exhaustion...
October 10, 2017: Immunity
https://www.readbyqxmd.com/read/29031045/structural-characterization-of-the-man5-glycoform-of-human-igg3-fc
#5
Ishan S Shah, Scott Lovell, Nurjahan Mehzabeen, Kevin P Battaile, Thomas J Tolbert
Immunoglobulin G (IgG) consists of four subclasses in humans: IgG1, IgG2, IgG3 and IgG4, which are highly conserved but have unique differences that result in subclass-specific effector functions. Though IgG1 is the most extensively studied IgG subclass, study of other subclasses is important to understand overall immune function and for development of new therapeutics. When compared to IgG1, IgG3 exhibits a similar binding profile to Fcγ receptors and stronger activation of complement. All IgG subclasses are glycosylated at N297, which is required for Fcγ receptor and C1q complement binding as well as maintaining optimal Fc conformation...
October 11, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29030308/engineering-intranasal-mrna-vaccines-to-enhance-lymph-node-trafficking-and-immune-responses
#6
Man Li, You Li, Ke Peng, Ying Wang, Tao Gong, Zhirong Zhang, Qin He, Xun Sun
Intranasal mRNA vaccination provides immediate immune protection against pandemic diseases. Recent studies have shown that diverse forms of polyethyleneimine (PEI) have potent mucosal adjuvant activity, which could significantly facilitate the delivery of intranasal mRNA vaccines. Nevertheless, optimizing the chemical structure of PEI to maximize its adjuvanticity and decrease its toxicity remains a challenge. Here we show that the chemical structure of PEI strongly influences how well nanocomplexes of PEI and mRNA migrate to the lymph nodes and elicit immune responses...
October 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29029399/a-cellular-platform-for-the-evaluation-of-immune-checkpoint-molecules
#7
Sabrina Jutz, Annika Hennig, Wolfgang Paster, Ömer Asrak, Dejana Dijanovic, Florian Kellner, Winfried F Pickl, Johannes B Huppa, Judith Leitner, Peter Steinberger
Blockade of the T cell coinhibitory molecules CTLA-4 and PD-1 has clinical utility to strengthen T cell responses. In addition to these immune checkpoints an ever-growing number of molecules has been implicated in generating coinhibitory signals in T cells. However, investigating coinhibitory molecules in primary human cells is complicated by the restricted expression and promiscuity of both coinhibitory receptors and their ligands. Here we have evaluated the potential of fluorescence-based transcriptional reporters based on the human Jurkat T cell line in conjunction with engineered T cell stimulator cell lines for investigating coinhibitory pathways...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29027713/engineering-cell-surface-function-with-dna-origami
#8
Ehsan Akbari, Molly Y Mollica, Christopher R Lucas, Sarah M Bushman, Randy A Patton, Melika Shahhosseini, Jonathan W Song, Carlos E Castro
A specific and reversible method is reported to engineer cell-membrane function by embedding DNA-origami nanodevices onto the cell surface. Robust membrane functionalization across epithelial, mesenchymal, and nonadherent immune cells is achieved with DNA nanoplatforms that enable functions including the construction of higher-order DNA assemblies at the cell surface and programed cell-cell adhesion between homotypic and heterotypic cells via sequence-specific DNA hybridization. It is anticipated that integration of DNA-origami nanodevices can transform the cell membrane into an engineered material that can mimic, manipulate, and measure biophysical and biochemical function within the plasma membrane of living cells...
October 13, 2017: Advanced Materials
https://www.readbyqxmd.com/read/29024301/emerging-principles-from-the-clinical-application-of-chimeric-antigen-receptor-car-t-cell-therapies-for-b-cell-malignancies
#9
REVIEW
Michael D Jain, Marco L Davila
Gene-engineered T cell therapies are soon to be FDA approved for at least two types of B cell malignancies in pediatric and adult patients, in the form of CD19 targeted chimeric antigen receptor T (CAR T) cell therapy. This represents a triumph of a true bench to bedside clinical translation of a therapy that was conceived of in the early 1990s. Clinical results have demonstrated efficacious responses in patients with the CD19 positive diseases B cell acute lymphoblastic leukemia (B-ALL) and diffuse large B cell lymphoma (DLBCL)...
October 11, 2017: Stem Cells
https://www.readbyqxmd.com/read/29023999/occupational-exposure-to-diesel-engine-exhaust-and-serum-cytokine-levels
#10
Yufei Dai, Dianzhi Ren, Bryan A Bassig, Roel Vermeulen, Wei Hu, Yong Niu, Huawei Duan, Meng Ye, Tao Meng, Jun Xu, Ping Bin, Meili Shen, Jufang Yang, Wei Fu, Kees Meliefste, Debra Silverman, Nathaniel Rothman, Qing Lan, Yuxin Zheng
The International Agency for Research on Cancer has classified diesel engine exhaust (DEE) as a human lung carcinogen. Given that inflammation is suspected to be an important underlying mechanism of lung carcinogenesis, we evaluated the relationship between DEE exposure and the inflammatory response using data from a cross-sectional molecular epidemiology study of 41 diesel engine testing workers and 46 unexposed controls. Repeated personal exposure measurements of PM2.5 and other DEE constituents were taken for the diesel engine testing workers before blood collection...
October 12, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29021918/protection-of-calves-by-a-prefusion-stabilized-bovine-rsv-f-vaccine
#11
Baoshan Zhang, Lei Chen, Chiara Silacci, Michelle Thom, Jeffrey C Boyington, Aliaksandr Druz, M Gordon Joyce, Efrain Guzman, Wing-Pui Kong, Yen-Ting Lai, Guillaume B E Stewart-Jones, Yaroslav Tsybovsky, Yongping Yang, Tongqing Zhou, Ulrich Baxa, John R Mascola, Davide Corti, Antonio Lanzavecchia, Geraldine Taylor, Peter D Kwong
Bovine respiratory syncytial virus, a major cause of respiratory disease in calves, is closely related to human RSV, a leading cause of respiratory disease in infants. Recently, promising human RSV-vaccine candidates have been engineered that stabilize the metastable fusion (F) glycoprotein in its prefusion state; however, the absence of a relevant animal model for human RSV has complicated assessment of these vaccine candidates. Here, we use a combination of structure-based design, antigenic characterization, and X-ray crystallography to translate human RSV F stabilization into the bovine context...
March 8, 2017: NPJ Vaccines
https://www.readbyqxmd.com/read/29020924/plant-jasmonate-zim-domain-genes-shedding-light-on-structure-and-expression-patterns-of-jaz-gene-family-in-sugarcane
#12
Feng Liu, Tingting Sun, Ling Wang, Weihua Su, Shiwu Gao, Yachun Su, Liping Xu, Youxiong Que
BACKGROUND: Sugarcane smut caused by Sporisorium scitamineum is one of the most severe fungal diseases in the sugarcane industry. Using a molecular biological technique to mine sugarcane resistance genes can provide gene resources for further genetic engineering of sugarcane disease-resistant breeding. Jasmonate ZIM (zinc-finger inflorescence meristem) domain (JAZ) proteins, which involved in the responses to plant pathogens and abiotic stresses, are important signaling molecules of the jasmonic acid (JA) pathway...
October 11, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29016556/the-current-status-and-future-of-cardiac-stem-progenitor-cell-therapy-for-congenital-heart-defects-from-diabetic-pregnancy
#13
REVIEW
Jianxiang Zhong, Shengbing Wang, Wei-Bin Shen, Sunjay Kaushal, Peixin Yang
Pregestational maternal diabetes induces congenital heart defects (CHDs). Cardiac dysfunction after palliative surgical procedures contributes to the high mortality of CHD patients. Autologous or allogeneic stem cell therapies are effective for improving cardiac function in animal models and clinical trials. c-kit(+) cardiac progenitor cells (CPCs), the most recognized CPCs, have the following basic properties of stem cells: self-renewal, multicellular clone formation, and differentiation into multiple cardiac lineages...
October 10, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28994323/atezolizumab-in-invasive-and-metastatic-urothelial-carcinoma
#14
Michael Crist, Arjun Balar
Until recently, there has been little advancement in the management of invasive and metastatic urothelial cancer in over 30 years, and outcomes with cisplatin-based chemotherapy remain unchanged. Inhibitors targeting PD-1 signaling on cytotoxic T-cells have revolutionized bladder cancer therapy leading to durable responses. Atezolizumab is an engineered humanized anti-PD-L1 monoclonal antibody that inhibits PD-L1 binding to PD-1 and B7.1, enhancing immune-mediated tumor killing and is currently approved as second-line treatment after failure of platinum-based chemotherapy as well as first-line in cisplatin-ineligible patients...
October 10, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28992509/liposomes-coated-gold-nanocages-with-antigens-and-adjuvants-targeted-delivery-to-dendritic-cells-for-enhancing-antitumor-immune-response
#15
Ruijing Liang, Jun Xie, Jun Li, Ke Wang, Liping Liu, Yujie Gao, Mubashir Hussain, Guanxin Shen, Jintao Zhu, Juan Tao
For nanovaccine-based cancer immunotherapy, dendritic cells (DCs) are one of the most powerful antigen presenting cells (APCs) that initiate and promote the maturation of antigen-specific cytotoxic T lymphocytes (e.g., CD8(+) T cells) to induce the local and systemic antitumor immunity and further suppress the tumor metastasis and produce long-term protection against tumor. Thus, the activation and maturation of DCs is the prerequisite for efficient CD8(+) T cell-based antitumor immune responses, which is considered as a primary and promising task for nanovaccine engineering...
September 26, 2017: Biomaterials
https://www.readbyqxmd.com/read/28990505/biological-therapy-of-hematologic-malignancies-toward-a-chemotherapy-free-era
#16
Pavel Klener, Tomas Etrych, Pavel Klener
Less than 70 years ago, the vast majority of hematologic malignancies were untreatable diseases with fatal prognoses. The development of modern chemotherapy agents, which had begun after the Second World War, was markedly accelerated by the discovery of the structure of DNA and its role in cancer biology and tumor cell division. The path travelled from the first temporary remissions observed in children with acute lymphoblastic leukemia treated with single-agent antimetabolites until the first cures achieved by multi-agent chemotherapy regimens was incredibly short...
October 6, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28989814/engineering-the-pre-metastatic-niche
#17
Brian A Aguado, Grace G Bushnell, Shreyas S Rao, Jacqueline S Jeruss, Lonnie D Shea
The pre-metastatic niche - the accumulation of aberrant immune cells and extracellular matrix proteins in target organs - primes the initially healthy organ microenvironment and renders it amenable for subsequent metastatic cell colonization. By attracting metastatic cancer cells, mimics of the pre-metastatic niche offer both diagnostic and therapeutic potential. However, deconstructing the complexity of the niche by identifying the interactions between cell populations and the mediatory roles of the immune system, soluble factors, extracellular matrix proteins, and stromal cells has proved challenging...
2017: Nature biomedical engineering
https://www.readbyqxmd.com/read/28989540/immunotheranostic-polymersomes-modularly-assembled-from-tetrablock-and-diblock-copolymers-with-oxidation-responsive-fluorescence
#18
Fanfan Du, Yu-Gang Liu, Evan Alexander Scott
INTRODUCTION: Intracellular delivery is a key step for many applications in medicine and for investigations into cellular function. This is particularly true for immunotherapy, which often requires controlled delivery of antigen and adjuvants to the cytoplasm of immune cells. Due to the complex responses generated by the stimulation of diverse immune cell populations, it is critical to monitor which cells are targeted during treatment. To address this issue, we have engineered an immunotheranostic polymersome delivery system that fluorescently marks immune cells following intracellular delivery...
October 2017: Cellular and Molecular Bioengineering
https://www.readbyqxmd.com/read/28986820/igg-fc-engineering-to-modulate-antibody-effector-functions
#19
REVIEW
Xinhua Wang, Mary Mathieu, Randall J Brezski
Therapeutic monoclonal antibodies are among the most effective biotherapeutics to date. An important aspect of antibodies is their ability to bind antigen while at the same time recruit immune effector functions. The majority of approved recombinant monoclonal antibody therapies are of the human IgG1 subclass, which can engage both humoral and cellular components of the immune system. The wealth of information generated about antibodies has afforded investigators the ability to molecularly engineer antibodies to modulate effector functions...
October 6, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28986672/high-accumulation-in-tobacco-seeds-of-hemagglutinin-antigen-from-avian-h5n1-influenza
#20
Yanaysi Ceballo, Kenia Tiel, Alina López, Gleysin Cabrera, Marlene Pérez, Osmany Ramos, Yamilka Rosabal, Carlos Montero, Rima Menassa, Ann Depicker, Abel Hernández
Tobacco seeds can be used as a cost effective system for production of recombinant vaccines. Avian influenza is an important respiratory pathogen that causes a high degree of mortality and becomes a serious threat for the poultry industry. A safe vaccine against avian flu produced at low cost could help to prevent future outbreaks. We have genetically engineered tobacco plants to express extracellular domain of hemagglutinin protein from H5N1 avian influenza virus as an inexpensive alternative for production purposes...
October 6, 2017: Transgenic Research
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