Alternative molecular formats and therapeutic applications for bispecific antibodies

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Single-Chain Antigen-Binding Proteins

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The therapeutic monoclonal antibody market

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Tumor Regression in Cancer Patients by Very Low Doses of a T Cell–Engaging Antibody

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Binding activities of a repertoire of single immunoglobulin variable domains secreted from Escherichia coli

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Biopharmaceutical benchmarks 2014

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Macromolecular Modeling with Rosetta

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Anti-Inflammatory Activity of Human IgG4 Antibodies by Dynamic Fab Arm Exchange

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Crystal Structure of a Neutralizing Human IgG Against HIV-1: A Template for Vaccine Design

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"Diabodies": small bivalent and bispecific antibody fragments.

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Therapeutic antibodies for autoimmunity and inflammation

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‘Knobs-into-holes’ engineering of antibody C H 3 domains for heavy chain heterodimerization

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Boosting Brain Uptake of a Therapeutic Antibody by Reducing Its Affinity for a Transcytosis Target

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Industrialization of mAb production technology: The bioprocessing industry at a crossroads

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Increased Brain Penetration and Potency of a Therapeutic Antibody Using a Monovalent Molecular Shuttle

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Strategies for extended serum half-life of protein therapeutics

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The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: Results of a prospective randomized phase II/III trial

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Crystal structure of a camel single-domain VH antibody fragment in complex with lysozyme

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A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model

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An efficient route to human bispecific IgG

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Hybrid antibodies can target sites for attack by T cells

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Immunoglobulin domain crossover as a generic approach for the production of bispecific IgG antibodies

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Dual targeting strategies with bispecific antibodies

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Variants of the Antibody Herceptin That Interact with HER2 and VEGF at the Antigen Binding Site

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Blinatumomab: A historical perspective

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A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity.

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Simultaneous targeting of multiple disease mediators by a dual-variable-domain immunoglobulin

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Identification and Multidimensional Optimization of an Asymmetric Bispecific IgG Antibody Mimicking the Function of Factor VIII Cofactor Activity

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Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange

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A Two-in-One Antibody against HER3 and EGFR Has Superior Inhibitory Activity Compared with Monospecific Antibodies

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Potent neutralization of botulinum neurotoxin by recombinant oligoclonal antibody

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Improved tumor targeting of anti–epidermal growth factor receptor Nanobodies through albumin binding: taking advantage of modular Nanobody technology

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Formatted anti–tumor necrosis factor α VHH proteins derived from camelids show superior potency and targeting to inflamed joints in a murine model of collagen‐induced arthritis

Coppieters, K. T., Dreier, T., Silence, K., de Haard, H., Lauwereys, M., Casteels, P., Beirnaert, E., Jonckheere, H., de Wiele, C. V., Staelens, L., et al. (2006) · Arthritis & Rheumatism · doi:10.1002/art.21827 · Cited by 303

Camel Single-domain Antibodies as Modular Building Units in Bispecific and Bivalent Antibody Constructs

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Selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving etanercept: a randomised clinical trial

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Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo

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Enhancing Antibody Fc Heterodimer Formation through Electrostatic Steering Effects

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Recombination of a mixture of univalent antibody fragments of different specificity

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Addressing Safety Liabilities of TfR Bispecific Antibodies That Cross the Blood-Brain Barrier

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Preparation and performance of bispecific F(ab' gamma)2 antibody containing thioether-linked Fab' gamma fragments.

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Stable heterodimers from remodeling the domain interface of a homodimer using a phage display library

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Preparation of Bispecific Antibodies by Chemical Recombination of Monoclonal Immunoglobulin G 1 Fragments

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Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent

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Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface

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Advances in the production and downstream processing of antibodies

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Improved Pharmacokinetics of Recombinant Bispecific Antibody Molecules by Fusion to Human Serum Albumin

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Stably tethered multifunctional structures of defined composition made by the dock and lock method for use in cancer targeting

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Bispecific tandem diabody for tumor therapy with improved antigen binding and pharmacokinetics

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Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies

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Effector Cell Recruitment with Novel Fv-based Dual-affinity Re-targeting Protein Leads to Potent Tumor Cytolysis and in Vivo B-cell Depletion

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SEEDbodies: fusion proteins based on strand-exchange engineered domain (SEED) CH3 heterodimers in an Fc analogue platform for asymmetric binders or immunofusions and bispecific antibodies†

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A Fully Human Recombinant IgG-like Bispecific Antibody to Both the Epidermal Growth Factor Receptor and the Insulin-like Growth Factor Receptor for Enhanced Antitumor Activity

Lu, D., Zhang, H., Koo, H., Tonra, J. R., Balderes, P. J., Prewett, M. C., Corcoran, E., Mangalampalli, V. R. M., Bassi, R., Anselma, D. J., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500815200 · Cited by 182

Development of humanized bispecific antibodies reactive with cytotoxic lymphocytes and tumor cells overexpressing the HER2 protooncogene.

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Targeting T cells to tumor cells using bispecific antibodies

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A tale of two specificities: bispecific antibodies for therapeutic and diagnostic applications

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A novel platform for engineering blood‐brain barrier‐crossing bispecific biologics

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Signal amplification in molecular imaging by pretargeting a multivalent, bispecific antibody

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Structural and functional characterization of the trifunctional antibody catumaxomab

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Generating Bispecific Human IgG1 and IgG2 Antibodies from Any Antibody Pair

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Antibody VH Domains as Small Recognition Units

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Phase I trial of 2B1, a bispecific monoclonal antibody targeting c-erbB-2 and Fc gamma RIII.

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Antibody therapeutics, antibody engineering, and the merits of protein stability.

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Chemical generation of bispecific antibodies

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Simultaneous Blockade of Both the Epidermal Growth Factor Receptor and the Insulin-like Growth Factor Receptor Signaling Pathways in Cancer Cells with a Fully Human Recombinant Bispecific Antibody

Lu, D., Zhang, H., Ludwig, D. L., Persaud, A., Jimenez, X., Burtrum, D. B., Balderes, P. J., Liu, M., Böhlen, P., Witte, L., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310132200 · Cited by 124

Improving biophysical properties of a bispecific antibody scaffold to aid developability

von Kreudenstein, T. S., Escobar-Cabrera, E., Lario, P. I., D’Angelo, I., Brault, K., Kelly, J. F., Durocher, Y., Baardsnes, J., Woods, R. J., Xie, M. H., et al. (2013) · mAbs · doi:10.4161/mabs.25632 · Cited by 123

Advantages of bispecific hybridomas in one-step immunocytochemistry and immunoassays.

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Engineering Aggregation-Resistant Antibodies

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Human Domain Antibodies against Virulence Traits ofCandida albicansInhibit Fungus Adherence to Vaginal Epithelium and Protect against Experimental Vaginal Candidiasis

Bernardis, F. D., Liu, H., O’Mahony, R., Valle, R. L., Bartollino, S., Sandini, S., Grant, S., Brewis, N., Tomlinson, I. M., Basset, R. C., et al. (2006) · The Journal of Infectious Diseases · doi:10.1086/509891 · Cited by 114

A novel tri-functional antibody fusion protein with improved pharmacokinetic properties generated by fusing a bispecific single-chain diabody with an albumin-binding domain from streptococcal protein G

Stork, R., Müller, D., & Kontermann, R. E. (2007) · Protein Engineering Design and Selection · doi:10.1093/protein/gzm061 · Cited by 111

Bispecific Designed Ankyrin Repeat Proteins (DARPins) Targeting Epidermal Growth Factor Receptor Inhibit A431 Cell Proliferation and Receptor Recycling

Boersma, Y. L., Chao, G., Steiner, D., Wittrup, K. D., & Plückthun, A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.293266 · Cited by 111

Sustained protection against Ebola virus infection following treatment of infected nonhuman primates with ZMAb

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Engineered proteins with desired specificity: DARPins, other alternative scaffolds and bispecific IgGs

Jost, C., & Plückthun, A. (2014) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2014.05.011 · Cited by 105

A novel bispecific antibody format enables simultaneous bivalent and monovalent co-engagement of distinct target antigens

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A modular IgG-scFv bispecific antibody topology

Orcutt, K. D., Ackerman, M. E., Cieslewicz, M., Quiroz, E., Slusarczyk, A. L., Frangioni, J. V., & Wittrup, K. D. (2009) · Protein Engineering Design and Selection · doi:10.1093/protein/gzp077 · Cited by 101

Molecular construction and optimization of anti-human IL-1α/β dual variable domain immunoglobulin (DVD-IgTM) molecules

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Cure of Burkitt's lymphoma in severe combined immunodeficiency mice by T cells, tetravalent CD3 x CD19 tandem diabody, and CD28 costimulation.

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Rational identification of an optimal antibody mixture for targeting the epidermal growth factor receptor

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Development of a Two-part Strategy to Identify a Therapeutic Human Bispecific Antibody That Inhibits IgE Receptor Signaling

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The Design and Characterization of Oligospecific Antibodies for Simultaneous Targeting of Multiple Disease Mediators

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Recombinant approaches to IgG-like bispecific antibodies

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Remodeling domain interfaces to enhance heterodimer formation

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Symmetry breaking: bispecific antibodies, the beginnings, and 50 years on.

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A Bispecific Diabody That Mediates Natural Killer Cell Cytotoxicity Against Xenotransplantated Human Hodgkin’s Tumors

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ImmTAC-redirected tumour cell killing induces and potentiates antigen cross-presentation by dendritic cells

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Four-in-One Antibodies Have Superior Cancer Inhibitory Activity against EGFR, HER2, HER3, and VEGF through Disruption of HER/MET Crosstalk

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