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Bispecific antibody

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https://www.readbyqxmd.com/read/28727448/extensive-survey-of-antibody-invariant-positions-for-efficient-chemical-conjugation-using-expanded-genetic-codes
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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/28692328/fabs-in-tandem-immunoglobulin-is-a-novel-and-versatile-bispecific-design-for-engaging-multiple-therapeutic-targets
#9
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
https://www.readbyqxmd.com/read/28691560/bispecific-antibody-therapy-in-hemophilia
#10
David Lillicrap
No abstract text is available yet for this article.
July 10, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28687600/pretargeted-imaging-and-therapy
#11
Mohamed Altai, Rosemery Membreno, Brendon Cook, Vladimir Tolmachev, Brian Zeglis
In vivo pretargeting stands as a promising approach to harnessing the exquisite tumor-targeting properties of antibodies for nuclear imaging and therapy while simultaneously skirting their pharmacokinetic limitations. The core premise of pretargeting lies in administering the targeting vector and radioisotope separately and having the two components combine within the body. In this manner, pretargeting strategies decrease the circulation time of the radioactivity, reduce the uptake of the radionuclide in healthy non-target tissues, and facilitate the use of short-lived radionuclides that would otherwise be incompatible with antibody-based vectors...
July 7, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28680755/bispecific-antibody-does-not-induce-t-cell-death-mediated-by-chimeric-antigen-receptor-against-disialoganglioside-gd2
#12
Sayed Shahabuddin Hoseini, Konstantin Dobrenkov, Dmitry Pankov, Xiaoliang L Xu, Nai-Kong V Cheung
Chimeric antigen receptors (CAR) and bispecific antibodies (BsAb) are two powerful immunotherapy approaches for retargeting lymphocytes toward cancer cells. Despite their success in lymphoblastic leukemia, solid tumors have been more recalcitrant. Identifying therapeutic barriers facing CAR-modified (CART) or BsAb-redirected T (BsAb-T) cells should facilitate their clinical translation to solid tumors. Novel lentiviral vectors containing low-affinity or high-affinity 4-1BB second-generation anti-GD2 (disialoganglioside) CARs were built to achieve efficient T cell transduction...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28679475/cik-as-therapeutic-agents-against-tumors
#13
REVIEW
M Introna
Cytokine Induced Killer (CIK) cells are ex vivo expanded and activated T lymphocytes obtained by sequential incubation of Peripheral Blood Mononuclear cells (PBMNC) with Interferon γ (IFNG), anti CD3 monoclonal antibody OKT3 and IL2. These cells, while retaining few characteristics of the Effector memory T cells subpopulation, acquired during culture CD56 expression, as well as non specific, Natural Killer like, anti tumoral cytotoxicity. CIK cells from human are equivalent to expanded NKT cells in mouse...
July 2, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28674296/next-generation-antibody-therapeutics-using-bispecific-antibody-technology
#14
Tomoyuki Igawa
 Nearly fifty monoclonal antibodies have been approved to date, and the market for monoclonal antibodies is expected to continue to grow. Since global competition in the field of antibody therapeutics is intense, we need to establish novel antibody engineering technologies to provide true benefit for patients, with differentiated product values. Bispecific antibodies are among the next generation of antibody therapeutics that can bind to two different target antigens by the two arms of immunoglobulin G (IgG) molecule, and are thus believed to be applicable to various therapeutic needs...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28669053/efficient-targeting-of-cd13-on-cancer-cells-by-the-immunotoxin-scfv13-eta-and-the-bispecific-scfv-13xds16
#15
Elena Grieger, Gerrit Gresch, Judith Niesen, Mira Woitok, Stefan Barth, Rainer Fischer, Rolf Fendel, Christoph Stein
PURPOSE: Treatment of cancer using standard chemotherapy still offers a poor prognosis combined with severe side effects. Novel antibody-based therapies have been shown to overcome low efficiency and lack of selectivity by targeting cancer-associated antigens, such as aminopeptidase CD13. METHODS: We isolated a high-affinity CD13-specific single-chain fragment variable (scFv13) from a phage display library of V-genes from mice immunized with soluble antigen. An immunotoxin comprising the scFv13 and a truncated version of the exotoxin A of Pseudomonas aeruginosa (ETA', scFv13-ETA') and a bispecific scFv targeting CD13 and CD16 simultaneously (bsscFv[13xds16]) was generated and investigated for their therapeutic potential...
July 1, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28664386/novel-therapies-for-acute-myeloid-leukemia-are-we-finally-breaking-the-deadlock
#16
REVIEW
Maximilian Stahl, Benjamin Y Lu, Tae Kon Kim, Amer M Zeidan
Acute myeloid leukemia (AML) is one of the best studied malignancies, and significant progress has been made in understanding the clinical implications of its disease biology. Unfortunately, drug development has not kept pace, as the '7+3' induction regimen remains the standard of care for patients fit for intensive therapy 40 years after its first use. Temporal improvements in overall survival were mostly confined to younger patients and driven by improvements in supportive care and use of hematopoietic stem cell transplantation...
June 29, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28659445/body-make-thy-own-bispecific-antibody
#17
(no author information available yet)
Synthetic mRNA that's been optimized, modified, and formulated to spur the production of bispecific antibodies in the liver can eradicate large tumors in mice. The strategy circumvents some of the manufacturing challenges associated with conventional antibody production and creates a therapeutic that's easier and more convenient to administer.
June 28, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28655766/a-new-approach-for-generating-bispecific-antibodies-based-on-a-common-light-chain-format-and-the-stable-architecture-of-human-immunoglobulin-g1
#18
Camilla De Nardis, Linda J A Hendriks, Emilie Poirier, Tudor Arvinte, Piet Gros, Alexander B H Bakker, John de Kruif
Bispecific antibodies combine two different antigen binding sites in a single molecule, enabling more specific targeting, novel mechanisms of action and higher clinical efficacies. Although they have the potential to outperform conventional monoclonal antibodies, many bispecific antibodies have issues regarding production, stability and pharmacokinetic properties. Here we describe a new approach for generating bispecific antibodies using a common light chain format and exploiting the stable architecture of human immunoglobulin G1...
June 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28637250/use-of-spytag-spycatcher-to-construct-bispecific-antibodies-that-target-two-epitopes-of-a-single-antigen
#19
Kyohei Yumura, Hiroki Akiba, Satoru Nagatoishi, Osamu Kusano-Arai, Hiroko Iwanari, Takao Hamakubo, Kouhei Tsumoto
Bispecific antibody targeting of two different antigens is promising, but when fragment-based antibodies are used, homogeneous production is difficult. To overcome this difficulty, we developed a method using the SpyTag/SpyCatcher system in which a covalent bond is formed between the two polypeptides. Using this method, we constructed a bispecific antibody that simultaneously interacted with two different epitopes of ROBO1, a membrane protein associated with cancer progression. A bispecific tetravalent antibody with an additional functional moiety was also constructed by using a dimeric biotin-binding protein...
June 16, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28634161/oncolytic-adenovirus-expressing-bispecific-antibody-targets-t-cell-cytotoxicity-in-cancer-biopsies
#20
Joshua D Freedman, Joachim Hagel, Eleanor M Scott, Ioannis Psallidas, Avinash Gupta, Laura Spiers, Paul Miller, Nikolaos Kanellakis, Rebecca Ashfield, Kerry D Fisher, Margaret R Duffy, Leonard W Seymour
Oncolytic viruses exploit the cancer cell phenotype to complete their lytic life cycle, releasing progeny virus to infect nearby cells and repeat the process. We modified the oncolytic group B adenovirus EnAdenotucirev (EnAd) to express a bispecific single-chain antibody, secreted from infected tumour cells into the microenvironment. This bispecific T-cell engager (BiTE) binds to EpCAM on target cells and cross-links them to CD3 on T cells, leading to clustering and activation of both CD4 and CD8 T cells. BiTE transcription can be controlled by the virus major late promoter, limiting expression to cancer cells that are permissive for virus replication...
June 20, 2017: EMBO Molecular Medicine
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