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https://www.readbyqxmd.com/read/29455062/enhanced-contraception-of-canine-zona-pellucida-3-dna-vaccine-via-targeting-dec-205-in-mice
#1
Ying Wang, Beibei Zhang, Jinyao Li, Adila Aipire, Yijie Li, Fuchun Zhang
Zona pellucida 3 (ZP3) is a potential antigen for the development of contraceptive vaccines to control animal population. In this study, we designed a canine ZP3 (CZP3) DNA vaccine through targeting DEC-205 (named as pcD-scFv-CZP3c) and investigated its contraceptive effect in mice. Female BALB/c mice were intramuscularly immunized 3 times at 2 weeks intervals. After immunization, humoral and cellular immune responses were detected by ELISA and flow cytometry. The results showed that pcD-CZP3 and pcD-scFv-CZP3c induced CZP3-specific antibody (Ab) responses both in serum and vaginal secretions compared to pcDNA3...
February 9, 2018: Theriogenology
https://www.readbyqxmd.com/read/29453518/chimeric-antigen-receptors-with-human-scfvs-preferentially-induce-t-cell-anti-tumor-activity-against-tumors-with-high-b7h6-expression
#2
Albert T Gacerez, Casey K Hua, Margaret E Ackerman, Charles L Sentman
B7H6 is emerging as a promising tumor antigen that is known to be expressed on a wide array of tumors and is reported to stimulate anti-tumor responses from the immune system. As such, B7H6 presents a good target for tumor-specific immunotherapies. B7H6-specific chimeric antigen receptors (CAR) based on a murine antibody showed successful targeting and elimination of tumors expressing B7H6. However, mouse single chain variable fragments (scFvs) have the potential to induce host anti-CAR responses that may limit efficacy, so human scFvs specific for B7H6 were selected by yeast surface display...
February 16, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29447266/engineered-resistance-to-nosema-bombycis-by-in-vitro-expression-of-a-single-chain-antibody-in-sf9-iii-cells
#3
Yukang Huang, Jie Chen, Bin Sun, Rong Zheng, Boning Li, Zeng Li, Yaoyao Tan, Junhong Wei, Guoqing Pan, Chunfeng Li, Zeyang Zhou
Nosema bombycis is a destructive, obligate intracellular parasite of the Bombyx mori. In this study, a single-chain variable fragment (scFv) dependent technology is developed for the purpose of inhibiting parasite proliferation in insect cells. The scFv-G4, which we prepared from a mouse G4 monoclonal antibody, can target the N. bombycis spore wall protein 12 (NbSWP12). Indirect immunofluorescence assays showed that NbSWP12 located mainly on the outside of the N. bombycis cytoskeleton, although some of it co-localized with β-tubulin in the meront-stage of parasites...
2018: PloS One
https://www.readbyqxmd.com/read/29438379/advancing-the-immunoaffinity-platform-affirm-to-targeted-measurements-of-proteins-in-serum-in-the-pg-ml-range
#4
Anna Säll, Daniel Corbee, Sara Vikström, Filip Ottosson, Helena Persson, Sofia Waldemarson
There is a great need for targeted protein assays with the capacity of sensitive measurements in complex samples such as plasma or serum, not the least for clinical purposes. Proteomics keeps generating hundreds of biomarker candidates that need to be transferred towards true clinical application through targeted verification studies and towards clinically applicable analysis formats. The immunoaffinity assay AFFIRM (AFFInity sRM) combines the sensitivity of recombinant single chain antibodies (scFv) for targeted protein enrichment with a specific mass spectrometry readout through selected reaction monitoring (SRM) in an automated workflow...
2018: PloS One
https://www.readbyqxmd.com/read/29436549/enhanced-delivery-of-sirna-to-triple-negative-breast-cancer-cells-in-vitro-and-in-vivo-through-functionalizing-lipid-coated-calcium-phosphate-nanoparticles-with-dual-target-ligands
#5
Jie Tang, Christopher B Howard, Stephen M Mahler, Kristofer J Thurecht, Leaf Huang, Zhi Ping Xu
The conjugation of ligands to nanoparticle platforms for the target delivery of therapeutic agents to the tumor tissue is one of the promising anti-cancer strategies. However, conventional nanoparticle platforms are not so effective in terms of the selectivity and transfection efficiency. In this study, we designed and developed a dual-target drug/gene delivery system based on lipid-coated calcium phosphate (LCP) nanoparticles (NPs) for significantly enhanced siRNA cellular uptake and transfection efficiency...
February 13, 2018: Nanoscale
https://www.readbyqxmd.com/read/29431047/car-t-cells-for-cancer-therapy
#6
Niaz Muhammad, Qinwen Mao, Haibin Xia
Chimeric antigen receptor (CAR) T-cells are redirected T-cells that can recognize cancer antigens in a major histocompatibility complex (MHC)-independent fashion. A typical CAR is comprised of two main functional domains: an extracellular antigen recognition domain, called a single-chain variable fragment (scFv), and an intracellular signaling domain. Based on the number of intracellular signaling molecules, CARs are categorized into four generations. CAR T-cell therapy has become a promising treatment for hematologic malignancies...
February 12, 2018: Biotechnology & Genetic Engineering Reviews
https://www.readbyqxmd.com/read/29427674/phage-display-antibodies-against-ectromelia-virus-that-neutralize-variola-virus-selection-and-implementation-for-p35-neutralizing-epitope-mapping
#7
Yana Khlusevich, Andrey Matveev, Ivan Baykov, Leonid Bulychev, Nikolai Bormotov, Ivan Ilyichev, Georgiy Shevelev, Vera Morozova, Dmitrii Pyshnyi, Nina Tikunova
In this study, five phage display antibodies (pdAbs) against ectromelia virus (ECTV) were selected from vaccinia virus (VACV)-immune phage-display library of human single chain variable fragments (scFv). ELISA demonstrated that selected pdAbs could recognize ECTV, VACV, and cowpox virus (CPXV). Atomic force microscopy visualized binding of the pdAbs to VACV. Three of the selected pdAbs neutralized variola virus (VARV) in the plaque reduction neutralization test. Western blot analysis of ECTV, VARV, VACV, and CPXV proteins indicated that neutralizing pdAbs bound orthopoxvirus 35 kDa proteins, which are encoded by the open reading frames orthologous to the ORF H3L in VACV...
February 7, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29420662/generation-of-high-affinity-internalizing-anti-fgfr2-single-chain-variable-antibody-fragment-fused-with-fc-for-targeting-gastrointestinal-cancers
#8
Aleksandra Borek, Aleksandra Sokolowska-Wedzina, Grzegorz Chodaczek, Jacek Otlewski
Fibroblast growth factor receptors (FGFRs) are promising targets for antibody-based cancer therapies, as their substantial overexpression has been found in various tumor cells. Aberrant activation of FGF receptor 2 (FGFR2) signaling through overexpression of FGFR2 and/or its ligands, mutations, or receptor amplification has been reported in multiple cancer types, including gastric, colorectal, endometrial, ovarian, breast and lung cancer. In this paper, we describe application of the phage display technology to produce a panel of high affinity single chain variable antibody fragments (scFvs) against the extracellular ligand-binding domain of FGFR2 (ECD_FGFR2)...
2018: PloS One
https://www.readbyqxmd.com/read/29420566/a-novel-monoclonal-antibody-targeting-carboxymethyllysine-an-advanced-glycation-end-product-in-atherosclerosis-and-pancreatic-cancer
#9
Ulrika Wendel, Nina Persson, Christian Risinger, Eva Bengtsson, Björn Nodin, Lena Danielsson, Charlotte Welinder, Gunilla Nordin Fredrikson, Bo Jansson, Ola Blixt
Advanced glycation end products are formed by non-enzymatic reactions between proteins and carbohydrates, causing irreversible lysine and arginine alterations that severely affect protein structure and function. The resulting modifications induce inflammation by binding to scavenger receptors. An increase in advanced glycation end products is observed in a number of diseases e.g. atherosclerosis and cancer. Since advanced glycation end products also are present in healthy individuals, their detection and quantification are of great importance for usage as potential biomarkers...
2018: PloS One
https://www.readbyqxmd.com/read/29416924/antitumor-effects-and-persistence-of-a-novel-her2-car-t-cells-directed-to-gastric-cancer-in-preclinical-models
#10
Yali Han, Chuanyong Liu, Guanhua Li, Juan Li, Xingyan Lv, Huan Shi, Jie Liu, Shuai Liu, Peng Yan, Shuyun Wang, Yuping Sun, Meili Sun
New immunotherapeutic approaches are urgently needed for gastric cancer due to its poor survival and unsatisfactory treatment. Here we applied the humanized chA21 scfv based chimeric antigen receptor (CAR) modified T cells approach to the HER2 overexpressing gastric cancer treatment. The chA21-4-1BBz CAR T cells specifically exerted Th1 skewed cytokine response and efficient cytolysis of HER2 overexpressing human gastric cancer cells in vitro . Both the cytokine production and cytotoxicity levels were correlated with the level of HER2 surface expression by tumor cells...
2018: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29415996/antitumor-activity-of-egfr-specific-car-t-cells-against-non-small-cell-lung-cancer-cells-in-vitro-and-in-mice
#11
He Li, Yao Huang, Du-Qing Jiang, Lian-Zhen Cui, Zhou He, Chao Wang, Zhi-Wei Zhang, Hai-Li Zhu, Yong-Mei Ding, Lin-Fang Li, Qiang Li, Hua-Jun Jin, Qi-Jun Qian
Effective control of non-small-cell lung cancer (NSCLC) remains clinically challenging, especially during advanced stages of the disease. This study developed an adoptive T-cell treatment through expression of a chimeric antigen receptor (CAR) to target human epidermal growth factor receptor (EGFR) in NSCLC. We optimized the non-viral piggyBac transposon system to engineer human T cells for the expression of EGFR-CAR, consisting of EGFR scFv, transmembrane domain, and intracellular 4-1BB-CD3ζ signaling domains...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29412489/preclinical-optimization-of-antibody-based-radiopharmaceuticals-for-cancer-imaging-and-radionuclide-therapy-model-vector-and-radionuclide-selection
#12
Lukas M Carter, Sophie Poty, Sai Kiran Sharma, Jason S Lewis
Intact antibodies and their truncated counterparts (e.g. Fab, scFv fragments) are generally exquisitely specific and selective vectors, enabling recognition of individual cancer-associated molecular phenotypes against a complex and dynamic biomolecular background. Complementary alignment of these advantages with unique properties of radionuclides is a defining paradigm in both radioimmunoimaging and radioimmunotherapy, which remain some of the most adept and promising tools for cancer diagnosis and treatment...
February 7, 2018: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29411237/cell-growth-inhibition-and-apoptosis-in-breast-cancer-cells-induced-by-anti-fzd7-scfvs-involvement-of-bioinformatics-based-design-of-novel-epitopes
#13
Neda Zarei, Mehdi Fazeli, Mozafar Mohammadi, Foroogh Nejatollahi
BACKGROUND: FZD7 has a critical role as a surface receptor of Wnt/β-catenin signaling in cancer cells. Suppressing Wnt signaling through blocking FZD7 is shown to decrease cell viability, metastasis and invasion. Bioinformatic methods have been a powerful tool in epitope designing studies. Small size, high affinity and human origin of scFv antibodies have provided unique advantages for these recombinant antibodies. METHODS: Two epitopes from extracellular domain of FZD7 were designed using bioinformatic methods...
February 6, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29399409/development-of-chimeric-antigen-receptors-targeting-t-cell-malignancies-using-two-structurally-different-anti-cd5-antigen-binding-domains-in-nk-and-crispr-edited-t-cell-lines
#14
Sunil S Raikar, Lauren C Fleischer, Robert Moot, Andrew Fedanov, Na Yoon Paik, Kristopher A Knight, Christopher B Doering, H Trent Spencer
Relapsed T-cell malignancies have poor outcomes when treated with chemotherapy, but survival after allogeneic bone marrow transplantation (BMT) approaches 50%. A limitation to BMT is the difficulty of achieving remission prior to transplant. Chimeric antigen receptor (CAR) T-cell therapy has shown successes in B-cell malignancies. This approach is difficult to adapt for the treatment of T-cell disease due to lack of a T-lymphoblast specific antigen and the fratricide of CAR T cells that occurs with T-cell antigen targeting...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29386504/adenoviral-vector-with-shield-and-adapter-increases-tumor-specificity-and-escapes-liver-and-immune-control
#15
Markus Schmid, Patrick Ernst, Annemarie Honegger, Maarit Suomalainen, Martina Zimmermann, Lukas Braun, Sarah Stauffer, Cristian Thom, Birgit Dreier, Matthias Eibauer, Anja Kipar, Viola Vogel, Urs F Greber, Ohad Medalia, Andreas Plückthun
Most systemic viral gene therapies have been limited by sequestration and degradation of virions, innate and adaptive immunity, and silencing of therapeutic genes within the target cells. Here we engineer a high-affinity protein coat, shielding the most commonly used vector in clinical gene therapy, human adenovirus type 5. Using electron microscopy and crystallography we demonstrate a massive coverage of the virion surface through the hexon-shielding scFv fragment, trimerized to exploit the hexon symmetry and gain avidity...
January 31, 2018: Nature Communications
https://www.readbyqxmd.com/read/29385713/nanobody-based-dual-specific-cars
#16
Stijn De Munter, Joline Ingels, Glenn Goetgeluk, Sarah Bonte, Melissa Pille, Karin Weening, Tessa Kerre, Hinrich Abken, Bart Vandekerckhove
Recent clinical trials have shown that adoptive chimeric antigen receptor (CAR) T cell therapy is a very potent and possibly curative option in the treatment of B cell leukemias and lymphomas. However, targeting a single antigen may not be sufficient, and relapse due to the emergence of antigen negative leukemic cells may occur. A potential strategy to counter the outgrowth of antigen escape variants is to broaden the specificity of the CAR by incorporation of multiple antigen recognition domains in tandem...
January 30, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29384367/tuning-the-hydrolytic-stability-of-next-generation-maleimide-cross-linkers-enables-access-to-albumin-antibody-fragment-conjugates-and-tri-scfvs
#17
Nafsika Forte, Maria Livanos, Enrique Miranda, Maurício Morais, Xiaoping Yang, Vineeth S Rajkumar, Kerry A Chester, Vijay Chudasama, James R Baker
We describe investigations to expand the scope of next generation maleimide cross-linkers for the construction of homogeneous protein-protein conjugates. Diiodomaleimides are shown to offer the ideal properties of rapid bioconjugation with reduced hydrolysis, allowing the cross-linking of even sterically hindered systems. The optimized linkers are exploited to link human serum albumin to antibody fragments (Fab or scFv) as a prospective half-life extension platform, with retention of antigen binding and robust serum stability...
January 31, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29377386/effect-of-linkers-on-immobilization-of-scfvs-with-biotin-streptavidin-interaction
#18
Svetlana P Ikonomova, Megan T Le, Neha Kalla, Amy J Karlsson
Single-chain variable fragment antibodies (scFvs) are attractive for use in applications that require high specificity and binding to a target, such as biosensors. Previously, we demonstrated that a variety of scFvs can be immobilized onto a streptavidin surface through in vivo biotinylation of the biotin carboxyl carrier protein (BCCP) or smaller AviTag fused to the scFvs. However, the BCCP constructs showed better immobilization than the AviTag constructs. In this work, we investigated whether the discrepancy between the biotinylation tags could be alleviated by incorporating flexible (G4 S)n linker of varying lengths or a rigid (EA3 K)3 linker between the biotinylation tags and the scFvs scFv13R4 and scFv5...
January 29, 2018: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/29376776/a-natively-paired-antibody-library-yields-drug-leads-with-higher-sensitivity-and-specificity-than-a-randomly-paired-antibody-library
#19
Adam S Adler, Daniel Bedinger, Matthew S Adams, Michael A Asensio, Robert C Edgar, Renee Leong, Jackson Leong, Rena A Mizrahi, Matthew J Spindler, Srinivasa Rao Bandi, Haichun Huang, Pallavi Tawde, Peter Brams, David S Johnson
Deep sequencing and single-chain variable fragment (scFv) yeast display methods are becoming more popular for discovery of therapeutic antibody candidates in mouse B cell repertoires. In this study, we compare a deep sequencing and scFv display method that retains native heavy and light chain pairing with a related method that randomly pairs heavy and light chain. We performed the studies in a humanized mouse, using interleukin 21 receptor (IL-21R) as a test immunogen. We identified 44 high-affinity binder scFv with the native pairing method and 100 high-affinity binder scFv with the random pairing method...
January 29, 2018: MAbs
https://www.readbyqxmd.com/read/29374508/re-engineering-and-evaluation-of-anti-dna-autoantibody-3e10-for-therapeutic-applications
#20
Zahra Rattray, Valentina Dubljevic, Nicholas J W Rattray, Deanne L Greenwood, Caroline H Johnson, James A Campbell, James E Hansen
A key challenge in the development of novel chemotherapeutics is the design of molecules capable of selective toxicity to cancer cells. Antibodies have greater target specificity compared to small molecule drugs, but most are unable to penetrate cells, and predominantly target extracellular antigens. A nuclear-penetrating anti-DNA autoantibody isolated from the MRL/lpr lupus mouse model, 3E10, preferentially localizes to tumors, inhibits DNA repair, and selectively kills cancer cells with defects in DNA repair...
January 24, 2018: Biochemical and Biophysical Research Communications
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