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https://www.readbyqxmd.com/read/28805498/gingiskhan%C3%A2-protease-cleavage-allows-a-high-throughput-antibody-to-fab-conversion-enabling-direct-functional-assessment-during-lead-identification-of-human-monoclonal-and-bispecific-igg1-antibodies
#1
Jörg Moelleken, Manuel Endesfelder, Christian Gassner, Sabine Lingke, Simone Tomaschek, Oksana Tyshchuk, Stefan Lorenz, Ulrike Reiff, Michael Mølhøj
The determination of the binding strength of immunoglobulins (IgGs) to targets can be influenced by avidity when the targets are soluble di- or multimeric proteins, or associated to cell surfaces, including surfaces introduced from heterogeneous assays. However, for the understanding of the contribution of a second drug-to-target binding site in molecular design, or for ranking of monovalent binders during lead identification, affinity-based assessment of the binding strength is required. Typically, monovalent binders like antigen-binding fragments (Fabs) are generated by proteolytic cleavage with papain, which often results in a combination of under- and over-digestion, and requires specific optimization and chromatographic purification of the desired Fabs...
August 14, 2017: MAbs
https://www.readbyqxmd.com/read/28803057/cross-reactivity-and-cross-immunomodulation-between-venoms-of-the-snakes-bothrops-asper-crotalus-simus-and-lachesis-stenophrys-and-its-effect-in-the-production-of-polyspecific-antivenom-for-central-america
#2
Cynthia Arroyo, Sergio Solano, Álvaro Segura, María Herrera, Ricardo Estrada, Mauren Villalta, Mariángela Vargas, José María Gutiérrez, Guillermo León
A mixture of the venoms of Bothrops asper, Crotalus simus and Lachesis stenophrys is used as immunogen to produce the polyspecific Central American antivenom (PoliVal-ICP). In this work, we studied the ability of each of these venoms to modulate the antibody response induced by the other two venoms included in the immunization mixture. For that, equine monospecific, bispecific and polyspecific antivenoms were prepared and compared regarding their ability to neutralize the phospholipase A2, coagulant and lethal activities of each venom, and their anti-venom antibodies concentration...
August 9, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28797938/bihc-a-t-cell-engaging-bispecific-recombinant-antibody-has-potent-cytotoxic-activity-against-her2-tumor-cells
#3
Jieyu Xing, Limin Lin, Jing Li, Jiayu Liu, Changhua Zhou, Haitao Pan, Rui Shu, Bin Dong, Donglin Cao, Qing Li, Zhong Wang
Among different cancer immunotherapy approaches, bispecific antibodies (BsAbs) are of great interest due to their ability to recruit immune cells to kill tumor cells directly. Various BsAbs against Her2 tumor cells have been proposed with potent cytotoxic activities. However, most of these formats require extensive processing to obtain heterodimeric bispecific antibodies. In this study, we describe a bispecific antibody, BiHC (bispecific Her2-CD3 antibody), constructed with a single-domain anti-Her2 and a single-chain Fv (variable fragment) of anti-CD3 in an IgG-like format...
August 7, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28794022/potent-in-vivo-nk-cell-mediated-elimination-of-hiv-1-infected-cells-mobilized-by-a-gp120-bispecific-and-hexavalent-broadly-neutralizing-fusion-protein
#4
Ariola Bardhi, Yanling Wu, Weizao Chen, Zhongyu Zhu, Jian Hua Zheng, Hing Wong, Emily Jeng, Jennifer Jones, Christina Ochsenbauer, John C Kappes, Dimiter S Dimitrov, Tianlei Ying, Harris Goldstein
Antibodies bound to HIV-1 envelope protein expressed by infected cells mobilize antibody dependent cellular cytotoxicity (ADCC) to eliminate the HIV-1-infected cells and thereby suppress HIV-1 infection and delay disease progression. Studies treating HIV-1-infected individuals with latency reactivation agents to reduce their latent HIV-1 reservoirs indicated that their HIV-1-specific immune responses were insufficient to effectively eliminate the reactivated latent HIV-1-infected T cells. Mobilization of ADCC may facilitate elimination of reactivated latent HIV-1-infected cells to deplete the HIV-1 reservoir and contribute to functional HIV-1 cure...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28790849/immunotargeting-relapsed-or-refractory-precursor-b-cell-acute-lymphoblastic-leukemia-role-of-blinatumomab
#5
REVIEW
Manon Queudeville, Rupert Handgretinger, Martin Ebinger
Patients with refractory or relapsed (R/R) acute lymphoblastic leukemia (ALL) have a dismal prognosis of around 5% long-term survival when treated with cytotoxic chemotherapy and allogenic stem cell transplantation. T-cell immunobased strategies open up new therapeutic perspectives. Blinatumomab is the first of a new class of antibody constructs that was labeled bispecific T-cell engager (BiTE): it consists of two single chain variable fragment connected with a flexible linker, one side binding CD3, the other CD19...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28765298/creation-of-recombinant-antibodies-using-degenerate-oligonucleotides-to-amplify-heavy-and-light-chain-sequences
#6
James R Dasch, Amy L Dasch
Recombinant antibodies can be modified to suit the application: Changes in isotype, format (e.g., scFv, Fab, bispecific antibodies), and specificity can be made once the heavy- and light-chain sequences are available. However, Ig gene families are large and the variable region gene segments are, indeed, variable, precluding the use of polymerase chain reaction (PCR) with two simple primers to amplify the heavy and light chain gene segments. A wide variety of approaches have been taken to obviate the complexity of the variable region gene segments, including using "universal" or degenerate primers...
August 1, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28765121/novel-therapies-for-immune-mediated-inflammatory-diseases-what-can-we-learn-from-their-use-in-rheumatoid-arthritis-spondyloarthritis-systemic-lupus-erythematosus-psoriasis-crohn-s-disease-and-ulcerative-colitis
#7
REVIEW
Kenneth F Baker, John D Isaacs
The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide...
August 1, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28757632/cancer-mrna-encoded-bispecific-antibodies-eliminate-tumours
#8
Sarah Crunkhorn
No abstract text is available yet for this article.
July 31, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28756350/immunotherapy-in-adult-acute-leukemia
#9
REVIEW
Sabine Blum, Filipe Martins, Michael Lübbert
The treatment of acute myeloid leukemia (AML) did not evolve profoundly in the last decades. Some improvement has been made for acute lymphoblastic leukemia (ALL). Emerging new treatment modalities, such as immunotherapy, are now beginning to be available for acute leukemia, mostly for patients suffering from ALL. This review aims to give an overview of these new therapeutic approaches, especially those already available. The focus is on cell-based immunotherapy, or molecules using preexisting host cells. Underlying mechanisms are explained and an overview of clinical experience with phase 1-3 studies is given...
June 29, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28751764/a-novel-bcma-cd3-bispecific-t-cell-engager-for-the-treatment-of-multiple-myeloma-induces-selective-lysis-in-vitro-and-in-vivo
#10
S Hipp, Y-T Tai, D Blanset, P Deegen, J Wahl, O Thomas, B Rattel, P J Adam, K C Anderson, M Friedrich
This corrects the article DOI: 10.1038/leu.2016.388.
July 28, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28727448/extensive-survey-of-antibody-invariant-positions-for-efficient-chemical-conjugation-using-expanded-genetic-codes
#11
Akifumi Kato, Mitsuo Kuratani, Tatsuo Yanagisawa, Kazumasa Ohtake, Akiko Hayashi, Yoshimi Amano, Kaname Kimura, Shigeyuki Yokoyama, Kensaku Sakamoto, Yasuhisa Shiraishi
The site-specific chemical conjugation of proteins, following synthesis with an expanded genetic code, promises to advance antibody-based technologies, including antibody drug conjugation and the creation of bispecific Fab dimers. The incorporation of non-natural amino acids into antibodies not only guarantees site specificity but also allows the use of bio-orthogonal chemistry. However, the efficiency of amino acid incorporation fluctuates significantly among different sites, thereby hampering the identification of useful conjugation sites...
July 20, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28726352/computational-design-of-a-specific-heavy-chain-%C3%AE%C2%BA-light-chain-interface-for-expressing-fully-igg-bispecific-antibodies
#12
K J Froning, A Leaver-Fay, X Wu, S Phan, L Gao, F Huang, A Pustilnik, M Bacica, K Houlihan, Q Chai, J R Fitchett, J Hendle, B Kuhlman, S J Demarest
The use of bispecific antibodies (BsAbs) to treat human diseases is on the rise. Increasingly complex and powerful therapeutic mechanisms made possible by BsAbs are being described in the literature and are spurring innovation of novel BsAb formats and methods for their production. The long-lived in vivo pharmacokinetics, optimal biophysical properties and potential effector functions of natural IgG monoclonal (and monospecific) antibodies has resulted in a push to generate fully IgG BsAb formats with the same quaternary structure as monoclonal IgGs...
July 20, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28725275/ash-meeting-2016-developments-in-hemostaseology
#13
REVIEW
Clemens Feistritzer, Birgit Mosheimer
During the annual meeting of the American Society of Hematology (ASH) in San Diego/California, novel developments in the field of hemostaseology were presented. Alternative treatment strategies besides factor replacement were discussed for patients with hemophilia. One of the highlights of the meeting in this year's plenary session was the presentation of successful adeno-associated virus mediated gene transfer in patients with hemophilia B leading to sustained elevation of factor IX:C (FIX:c). Other alternative treatment approaches in patients with hemophilia A may include bispecific antibodies mimicking factor VIIIa (FVIIIa) activity or disrupting anticoagulant proteins...
2017: Memo
https://www.readbyqxmd.com/read/28722325/polymer-mediated-flocculation-of-transient-cho-cultures-as-a-simple-high-throughput-method-to-facilitate-antibody-discovery
#14
Matthew G Schmitt, Yashas Rajendra, Maria D Hougland, Jeffrey S Boyles, Gavin C Barnard
Most biopharmaceutical drugs, especially monoclonal antibodies (mAbs), bispecific antibodies (BsAbs) and Fc-fusion proteins, are expressed using Chinese Hamster Ovary (CHO) cell lines. CHO cells typically yield high product titers and high product quality. Unfortunately, CHO cell lines also generate high molecular weight (HMW) aggregates of the desired product during cell culture along with CHO host cell protein (HCP) and CHO DNA. These immunogenic species, co-purified during Protein A purification, must be removed in a multi-step purification process...
July 19, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28720505/chemically-generated-igg2-bispecific-antibodies-through-disulfide-bridging
#15
James T Patterson, Edwige Gros, Heyue Zhou, Ghazi Atassi, Lisa Kerwin, Lisa Carmody, Tong Zhu, Bryan Jones, Yanwen Fu, Gunnar F Kaufmann
Bispecific antibodies (BsAbs) are designed to engage two antigens simultaneously, thus, effectively expanding the ability of antibody-based therapeutics to target multiple pathways within the same cell, engage two separate soluble antigens, bind the same antigen with distinct paratopes, or crosslink two different cell types. Many recombinant BsAb formats have emerged, however, expression and purification of such constructs can often be challenging. To this end, we have developed a chemical strategy for generating BsAbs using native IgG2 architecture...
July 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28714211/modeling-of-bispecific-antibody-elution-in-mixed-mode-cation-exchange-chromatography
#16
Yi Feng Lee, Simon Kluters, Mirjam Hillmann, Thomas von Hirschheydt, Christian Frech
The increasing demand for cost-efficient manufacturing of biopharmaceuticals has been the main driving force for the development of novel chromatography resins, which resulted in the development of multimodal or mixed-mode chromatographic resins. Most of them combine electrostatic and hydrophobic functionalities and are designed to deliver unique selectivity and increased binding capacities also at increased ionic strength. However, the mechanism of the protein-resin interaction in mixed-mode chromatography is still not fully understood...
July 17, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/28712395/-inhibitory-effect-of-bispecific-antibody-targeting-il-12-p40-and-tnf-%C3%AE-simultaneously-on-psoriasis-in-mice
#17
Pin Xu, Ni Xie, Caiguo Ye
Objective To construct bispecific antibodies, which can block interleukin 12 (IL-12)/IL-23 p40 subunit and tumor necrosis factor α (TNF-α) simultaneously, and identify their biological function and inhibitory effect on psoriasis formation in mice. Methods Based on the sequences of adalimumab and ustekinumab, three kinds of bispecific antibodies were designed, named BiAU003, BiAU022 and BiAU023. The specificity and binding capacity of bispecific antibodies were determined by ELISA. After co-treated with bispecific antibodies and TNF-α, the level of endothelial leukocyte adhesion molecule-1 (ELMA-1) labeled with fluorescein isothiocyanate (FITC) in human umbilical vein endothelial cells (HUVECs) were examined by flow cytometry...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28705917/curative-multi-cycle-radioimmunotherapy-monitored-by-quantitative-spect-ct-based-theranostics-using-bispecific-antibody-pretargeting-strategy-in-colorectal-cancer
#18
Sarah M Cheal, Edward K Fung, Miteshkumar V Patel, Blesida Punzalan, Hong Xu, Hong-Fen Guo, Pat B Zanzonico, Sebastien Monette, Karl Dane Wittrup, Nai-Kong Cheung, Steven M Larson
Radioimmunotherapy of solid tumors using antibody-targeted radionuclides has been limited by low therapeutic indices (TI). We recently reported a novel three-step pretargeted radioimmunotherapy (PRIT) strategy based on a glycoprotein A33 (GPA33)-targeting bispecific antibody (bsAb) and a small-molecule radioactive hapten, a complex of lutetium-177 ((177)Lu) and S-2-(4-aminobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid ((177)Lu-DOTA-Bn) that leads to high TIs for radiosensitive tissues such as blood (TI = 73) and kidney (TI = 12)...
July 13, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28700541/merck-kgaa-f-star-shake-on-immune-oncology-bispecifics
#19
(no author information available yet)
No abstract text is available yet for this article.
July 12, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28692328/fabs-in-tandem-immunoglobulin-is-a-novel-and-versatile-bispecific-design-for-engaging-multiple-therapeutic-targets
#20
Shiyong Gong, Fang Ren, Danqing Wu, Xuan Wu, Chengbin Wu
In recent years, the development of bispecific antibody (bsAb) has become a major trend in the biopharmaceutical industry. By simultaneously engaging two molecular targets, bsAbs show unique mechanisms of action that could lead to clinical benefits unattainable by conventional monoclonal antibodies. Various bsAb generation formats have been described, and several are being investigated in clinical development. However, some bsAb constructs have proven to be problematic due to their unfavorable physicochemical and pharmacokinetic properties, as well as poor manufacturing efficiencies...
July 10, 2017: MAbs
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