keyword
MENU ▼
Read by QxMD icon Read
search

bispecific scFv

keyword
https://www.readbyqxmd.com/read/27697033/recombinant-antibody-fragments-for-neurodegenerative-diseases
#1
Karen Manoutcharian, Roxanna Perez-Garmendia, Goar Gevorkian
Recombinant antibody fragments are promising alternatives to full-length immunoglobulins and offer important advantages compared with conventional monoclonal antibodies: extreme specificity, higher affinity, superior stability and solubility, reduced immunogenicity as well as easy and inexpensive large-scale production. Different antibody formats such as single-chain fragment variable (scFv), single-domain antibody fragments (VHHs or sdAbs), bispecific antibodies (bsAbs), intrabodies and nanobodies, are currently being studied in pre-clinical models of cancer as well as infectious and autoimmune diseases and many of them are being tested as therapeutics in clinical trials...
September 30, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/27650544/tetraspecific-scfv-construct-provides-nk-cell-mediated-adcc-and-self-sustaining-stimuli-via-insertion-of-il-15-as-a-cross-linker
#2
Joerg U Schmohl, Martin Felices, Deborah Todhunter, Elizabeth Taras, Jeffrey S Miller, Daniel A Vallera
BACKGROUND: The design of a highly effective anti-cancer immune-engager would include targeting of highly drug refractory cancer stem cells (CSC). The design would promote effective antibody-dependent cell-mediated cytotoxicity (ADCC) and simultaneously promote costimulation to expand and self-sustain the effector NK cell population. Based on our bispecific NK cell engager platform we constructed a tetraspecific killer engager (TetraKE) comprising single-chain variable fragments (scFvs) binding FcγRIII (CD16) on NK cells, EpCAM on carcinoma cells and CD133 on cancer stem cells in order to promote ADCC...
September 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27590740/comparative-analysis-of-bispecific-antibody-and-streptavidin-targeted-radioimmunotherapy-for-b-cell-cancers
#3
Damian J Green, Shani L Frayo, Yukang Lin, Donald K Hamlin, Darrell R Fisher, Sofia Hl Frost, Aimee L Kenoyer, Mark D Hylarides, Ajay K Gopal, Ted A Gooley, Johnnie J Orozco, Brian G Till, Shyril O'Steen, Kelly D Orcutt, D Scott Wilbur, K Dane Wittrup, Oliver W Press
Streptavidin (SA)-biotin pretargeted radioimmunotherapy (PRIT) that targets CD20 in non-Hodgkin lymphoma (NHL) exhibits remarkable efficacy in model systems, but SA immunogenicity and interference by endogenous biotin may complicate clinical translation of this approach. In this study, we engineered a bispecific fusion protein (FP) that evades the limitations imposed by this system. Briefly, one arm of the FP was an anti-human CD20 antibody (2H7) with the other arm of the FP an anti-chelated radiometal trap for a radiolabeled ligand (yttrium[Y]-DOTA) captured by a very high-affinity anti-Y-DOTA scFv antibody (C825)...
September 2, 2016: Cancer Research
https://www.readbyqxmd.com/read/27471647/successful-engineering-of-a-highly-potent-single-chain-variable-fragment-scfv-bispecific-antibody-to-target-disialoganglioside-gd2-positive-tumors
#4
Ming Cheng, Brian H Santich, Hong Xu, Mahiuddin Ahmed, Morgan Huse, Nai-Kong V Cheung
Engineering potent bispecific antibodies from single-chain variable fragments (scFv) remains difficult due to the inherent instability and insufficient binding of scFv's compared to their parental immunoglobulin format. Previously, we described a scFv-based bispecific antibody (scBA) against disialoganglioside (GD2) based on the anti-GD2 murine 5F11-scFv and the anti-CD3 huOKT3-scFv (5F11-scBA). In this study, we substituted the 5F11-scFv with the higher affinity (13-fold) hu3F8-scFv to form hu3F8-scBA. With this modification, hu3F8-scBA redirected T cells to kill GD2(+) cancer cell lines with up to 5,000-fold higher potency (femtomolar EC50) compared with 5F11-scBA (picomolar EC50) in cytotoxicity assays, even against target cells with low GD2 densities...
June 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27427982/tandem-car-t-cells-targeting-her2-and-il13r%C3%AE-2-mitigate-tumor-antigen-escape
#5
Meenakshi Hegde, Malini Mukherjee, Zakaria Grada, Antonella Pignata, Daniel Landi, Shoba A Navai, Amanda Wakefield, Kristen Fousek, Kevin Bielamowicz, Kevin K H Chow, Vita S Brawley, Tiara T Byrd, Simone Krebs, Stephen Gottschalk, Winfried S Wels, Matthew L Baker, Gianpietro Dotti, Maksim Mamonkin, Malcolm K Brenner, Jordan S Orange, Nabil Ahmed
In preclinical models of glioblastoma, antigen escape variants can lead to tumor recurrence after treatment with CAR T cells that are redirected to single tumor antigens. Given the heterogeneous expression of antigens on glioblastomas, we hypothesized that a bispecific CAR molecule would mitigate antigen escape and improve the antitumor activity of T cells. Here, we created a CAR that joins a HER2-binding scFv and an IL13Rα2-binding IL-13 mutein to make a tandem CAR exodomain (TanCAR) and a CD28.ζ endodomain...
August 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27419146/overcoming-the-constraints-of-anti-hiv-cd89-bispecific-antibodies-that-limit-viral-inhibition
#6
Xiaocong Yu, Mark Duval, Melissa Gawron, Marshall R Posner, Lisa A Cavacini
Innovative strategies are necessary to maximize the clinical application of HIV neutralizing antibodies. To this end, bispecific constructs of human antibody F240, reactive with well-conserved gp41 epitope and antibody 14A8, reactive with the IgA receptor (CD89) on effector cells, were constructed. A F240 × 14A8 bispecific single chain variable region (scFv) molecule was constructed by linking two scFvs using a conventional GGGGS linker. Despite immunoreactivity with HIV gp41 and neutrophils, this bispecific scFv failed to inhibit HIV infection...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27220396/construction-and-functional-analysis-of-an-anti-human-cervical-carcinoma-anti-human-cd3-single-chain-bispecific-antibody
#7
Hong Wu, Li Yao, Lin Chou, Jin-Hua Yang, Yun-Xiu Zhang, Xiao-Li Li, Bo-Er Shan
The aim of the present study was to construct a single-chain bispecific antibody (scBsAb) against cervical carcinoma and to investigate its biological activities. The scBsAb was constructed using a genetic cloning technique and antigen binding activities were detected by ELISA. The iodogen method was used to analyze the pharmacokinetics. The Rosette formation test was used to detect the binding ability between peripheral blood lymphocytes (PBLs) and Cs1213 cervical cancer cells. In addition, the MTT method was performed to detect the killing effect of PBLs...
July 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27157665/enhanced-adcc-and-nk-cell-activation-of-an-anticarcinoma-bispecific-antibody-by-genetic-insertion-of-a-modified-il-15-cross-linker
#8
Joerg U Schmohl, Martin Felices, Elizabeth Taras, Jeff S Miller, Daniel A Vallera
Previously, we constructed a bispecific NK-cell-engager (BiKE) bearing single-chain variable fragments (scFv) against CD16 on NK cells and EpCAM on tumor cells. This BiKE facilitated antigen-specific antibody-dependent cell-mediated cytotoxicity (ADCC) but did not induce NK cell expansion. We incorporated a modified interleukin-15 cross-linker to create a trispecific construct (TriKE) in order to improve activation, proliferation, and survival of NK cells. Synthesis and assembly of hybrid genes encoding the TriKE was accomplished using DNA-shuffling and DNA-ligation techniques...
August 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/27141353/characterization-of-the-first-in-class-t-cell-engaging-bispecific-single-chain-antibody-for-targeted-immunotherapy-of-solid-tumors-expressing-the-oncofetal-protein-claudin-6
#9
Christiane R Stadler, Hayat Bähr-Mahmud, Laura M Plum, Kathrin Schmoldt, Anne C Kölsch, Özlem Türeci, Ugur Sahin
The fetal tight junction molecule claudin 6 (CLDN6) is virtually absent from any normal tissue, whereas it is aberrantly and frequently expressed in various cancers of high medical need. We engineered 6PHU3, a T-cell-engaging bispecific single chain molecule (bi-(scFv)2) with anti-CD3/anti-CLDN6 specificities, and characterized its pharmacodynamic properties. Our data show that upon engagement by 6PHU3, T cells strongly upregulate cytotoxicity and activation markers, proliferate and acquire an effector phenotype...
March 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27111637/aberrant-bispecific-antibody-pharmacokinetics-linked-to-liver-sinusoidal-endothelium-clearance-mechanism-in-cynomolgus-monkeys
#10
Amita Datta-Mannan, Johnny E Croy, Linda Schirtzinger, Stacy Torgerson, Matthew Breyer, Victor J Wroblewski
Bispecific antibodies (BsAbs) can affect multiple disease pathways, thus these types of constructs potentially provide promising approaches to improve efficacy in complex disease indications. The specific and non-specific clearance mechanisms/biology that affect monoclonal antibody (mAb) pharmacokinetics are likely involved in the disposition of BsAbs. Despite these similarities, there are a paucity of studies on the in vivo biology that influences the biodistribution and pharmacokinetics of BsAbs. The present case study evaluated the in vivo disposition of 2 IgG-fusion BsAb formats deemed IgG-ECD (extracellular domain) and IgG-scFv (single-chain Fv) in cynomolgus monkeys...
July 2016: MAbs
https://www.readbyqxmd.com/read/27040766/tetravalent-anti-cd20-cd3-bispecific-antibody-for-the-treatment-of-b-cell-lymphoma
#11
Chia-Yen Lu, Gregory J Chen, Pei-Han Tai, Yu-Chen Yang, Yu-Shen Hsu, Mingi Chang, Chuan-Lung Hsu
Bispecific antibodies (bsAbs) are second generation antibodies for therapeutic application in immunotherapy. One of the major strategies of the bsAb platform is the recruitment of immune effector T cells by incorporating an anti-CD3 domain. A bispecific T-cell engager (BiTE), with one end having an affinity for CD3 and the other end with affinity for CD19, has been approved in the US and Europe for the treatment of acute lymphoblastic leukemia. However, due to their small size and lack of Fc region, these single-chain variable fragment (scFv) bsAbs have short half-lives in vivo...
May 13, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26954291/anti-human-cd138-monoclonal-antibodies-and-their-bispecific-formats-generation-and-characterization
#12
Dan Chen, Jianxuan Zou, Yunhui Zong, Huimin Meng, Gangli An, Lin Yang
Syndecan-1 (CD138), a heparan sulfate proteoglycan, acts as a co-receptor for growth factors and chemokines and is a molecular marker associated with the epithelial-mesenchymal transition during development and carcinogenesis. In this study, we generated two specific mouse anti-human CD138 monoclonal antibodies (mAbs, clone ID: 480CT5.4.3, 587CT7.3.6.5) using hybridoma technology and identified their immunological characteristics. After hybridoma sequencing, the single-chain variable fragments (ScFvs) cloned from two hybridoma cells were combined with anti-CD3 OKT-3 ScFv to generate two recombinant bispecific antibodies (h-STL002, m-STL002) against CD138 and CD3 molecules, respectively...
June 2016: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/26898800/a-bispecific-antibody-scbsabagn-2-tspo-target-for-ang-2-and-tspo-resulted-in-therapeutic-effects-against-glioblastomas
#13
Jia Li, Zhiming Zhang, Lianjie Lv, Haibo Qiao, Xiuju Chen, Changlin Zou
Antibody-based targeted therapy of cancers requires the antibody targeting of specific molecules inducing tumor cells apoptosis or death. Angiopoietin-2 (Agn-2) and translocator protein (TSPO) are identified as potential target molecules for glioblastoma therapy. The single chain anti-Agn-2 antibody (Anag-2) and anti-TSPO antibody (ATSPO) were obtained by monoclonal antibody screening. In the present study, for specific targeting and killing, we generated a recombinant bispecific antibody comprising a single-chain Fragment variable (ScFv) of anti-human Agn-2 and anti-human TSPO (ScBsAbAgn-2/TSPO), which is the mediator for mitochondrial apoptosis and tumor angiogenesis...
April 1, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26847056/il15-trispecific-killer-engagers-trike-make-natural-killer-cells-specific-to-cd33-targets-while-also-inducing-persistence-in-vivo-expansion-and-enhanced-function
#14
Daniel A Vallera, Martin Felices, Ron McElmurry, Valarie McCullar, Xianzheng Zhou, Joerg Uwe Schmohl, Bin Zhang, Alexander J Lenvik, Angela Panoskaltsis-Mortari, Michael R Verneris, Jakub Tolar, Sarah Cooley, Daniel J Weisdorf, Bruce R Blazar, Jeffrey S Miller
PURPOSE: The effectiveness of NK cell infusions to induce leukemic remission is limited by lack of both antigen specificity and in vivo expansion. To address the first issue, we previously generated a bispecific killer engager (BiKE) containing single-chain scFv against CD16 and CD33 to create an immunologic synapse between NK cells and CD33(+) myeloid targets. We have now incorporated a novel modified human IL15 crosslinker, producing a 161533 trispecific killer engager (TriKE) to induce expansion, priming, and survival, which we hypothesize will enhance clinical efficacy...
July 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/26791237/a-bispecific-protein-rg7s-mica-recruits-natural-killer-cells-and-enhances-nkg2d-mediated-immunosurveillance-against-hepatocellular-carcinoma
#15
Tong Wang, Fumou Sun, Wei Xie, Mingying Tang, Hua He, Xuelian Jia, Xuemei Tian, Min Wang, Juan Zhang
MHC class I-related chain A (MICA) is a principal immunoligand of the natural killer (NK) cell receptor NK group 2, member D (NKG2D) and plays a key role in NK cell-mediated immune recognition. Shedding of MICA from tumor cells leads to immunosuppression. To reconstitute the immunosurveilance function of NK cells, we constructed a fusion protein rG7S-MICA and explored its potential anti-tumor activity against hepatocellular carcinoma (HCC). rG7S-MICA consists of human MICA and a single-chain antibody fragment (scFv) targeting the tumor-associated antigen cluster of differentiation 24 (CD24)...
March 28, 2016: Cancer Letters
https://www.readbyqxmd.com/read/26596724/theranostic-pretargeted-radioimmunotherapy-of-colorectal-cancer-xenografts-in-mice-using-picomolar-affinity-%C3%A2-%C3%A2-y-or-%C3%A2-%C3%A2-%C3%A2-lu-dota-bn-binding-scfv-c825-gpa33-igg-bispecific-immunoconjugates
#16
Sarah M Cheal, Hong Xu, Hong-Fen Guo, Sang-Gyu Lee, Blesida Punzalan, Sandhya Chalasani, Edward K Fung, Achim Jungbluth, Pat B Zanzonico, Jorge A Carrasquillo, Joseph O'Donoghue, Peter M Smith-Jones, K Dane Wittrup, Nai-Kong V Cheung, Steven M Larson
PURPOSE: GPA33 is a colorectal cancer (CRC) antigen with unique retention properties after huA33-mediated tumor targeting. We tested a pretargeted radioimmunotherapy (PRIT) approach for CRC using a tetravalent bispecific antibody with dual specificity for GPA33 tumor antigen and DOTA-Bn-(radiolanthanide metal) complex. METHODS: PRIT was optimized in vivo by titrating sequential intravenous doses of huA33-C825, the dextran-based clearing agent, and the C825 haptens (177)Lu-or (86)Y-DOTA-Bn in mice bearing the SW1222 subcutaneous (s...
May 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/26571693/-expression-and-characterization-of-a-bispecific-antibody-targeting-tnf-%C3%AE-and-ed-b-containing-fibronectin
#17
Xueping Hu, Mian Xie, Lujun Li, Sijing Jiang, Mengyuan Liu
To enhance the specificity of anti-TNF-α single chain Fv antibody (TNF-scFv) to inflamed site, we constructed a bispecific antibody BsDb that targets TNF-α and ED-B-containing fibronectin (B-FN) by covalently linking TNF-scFv and the anti-ED-B scFv L19 at the gene level via a flexible peptide linker deriving from human serum albumin. BsDb was successfully secreted from Pichia pastoris as functional protein, identified by immunoblotting, and purified to homogeneity with affinity chromatography. BsDb retained the immunoreactivity of its original antibodies TNF-scFv and L19, and showed a marked gain in antigen-binding affinity and in TNF-α-neutralizing ability, when compared to TNF-scFv and L19 that were produced in Escherichia coli...
May 2015: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/26469402/large-scale-purification-of-r28m-a-bispecific-scfv-antibody-targeting-human-melanoma-produced-in-transgenic-cattle
#18
Katrin Spiesberger, Florian Paulfranz, Anton Egger, Judith Reiser, Claus Vogl, Judith Rudolf-Scholik, Corina Mayrhofer, Ludger Grosse-Hovest, Gottfried Brem
BACKGROUND: 30 years ago, the potential of bispecific antibodies to engage cytotoxic T cells for the lysis of cancer cells was discovered. Today a variety of bispecific antibodies against diverse cell surface structures have been developed, the majority of them produced in mammalian cell culture systems. Beside the r28M, described here, no such bispecific antibody is known to be expressed by transgenic livestock, although various biologicals for medical needs are already harvested-mostly from the milk-of these transgenics...
2015: PloS One
https://www.readbyqxmd.com/read/26430884/a-fab-selective-immunoglobulin-binding-domain-from-streptococcal-protein-g-with-improved-half-life-extension-properties
#19
Felix Unverdorben, Meike Hutt, Oliver Seifert, Roland E Kontermann
BACKGROUND: Half-life extension strategies have gained increasing interest to improve the pharmacokinetic and pharmacodynamic properties of protein therapeutics. Recently, we established an immunoglobulin-binding domain (IgBD) from streptococcal protein G (SpGC3) as module for half-life extension. SpGC3 is capable of binding to the Fc region as well as the CH1 domain of Fab arms under neutral and acidic conditions. METHODOLOGY/PRINCIPAL FINDINGS: Using site-directed mutagenesis, we generated a Fab-selective mutant (SpGC3Fab) to avoid possible interference with the FcRn-mediated recycling process and improved its affinity for mouse and human IgG by site-directed mutagenesis and phage display selections...
2015: PloS One
https://www.readbyqxmd.com/read/26246000/effects-of-different-interchain-linkers-on-biological-activity-of-an-anti-prostate-cancer-single-chain-bispecific-antibody
#20
Chao-hui Hao, Qian-he Han, Zhong-jie Shan, Jian-ting Hu, Nan Zhang, Xue-pei Zhang
BACKGROUND: A single-chain bispecific antibody (scBsAb; an engineered antibody), has promising clinical applications. Nonetheless, the effect of different interchain linkers on its activity is poorly understood. METHODS: Gene synthesis was used to splice the anti-γ-seminoprotein single-chain antibody (anti-γ-Sm scFv) gene with the anti-CD3 single-chain antibody (anti-CD3 scFv) gene via different interchain peptide linkers. The Phyre2 software was used to predict spatial configuration of different scBsAbs...
2015: Theoretical Biology & Medical Modelling
keyword
keyword
78244
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"