Therapeutic bispecific antibody formats: a patent applications review (1994-2017)

Godar, Marie; Haard, Hans de; Blanchetot, Christophe; Rasser, Jacobus

doi:10.1080/13543776.2018.1428307

Cited by 45 publications

(41 citation statements)

References 91 publications

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“…Multiple other Fc engineering approaches have been described for fine tuning the effector functions and blood half-life (Saxena and Wu, 2016). Additionally, antibodies can be made as bispecific molecules to specifically recognize two different epitopes or as antibody-drug conjugates for the targeted delivery of cytotoxic agents, enabling additional therapeutic modalities (Beck et al, 2017;Godar et al, 2018).…”

Section: Targeting Cxcr4 and Ackr3 With Antibodiesmentioning

confidence: 99%

“…By this means, active and/or inactive conformations of different receptors have been obtained. Targets thus far include the b 2 adrenergic receptor, M 2 muscarinic acetylcholine receptor, m-opioid receptor, k-opioid receptor, and the viral chemokine receptor US28 (Rasmussen et al, 2007(Rasmussen et al, , 2011Kruse et al, 2013;Ring et al, 2013;Burg et al, 2015;Huang et al, 2015;Godar et al, 2018). The use of stabilizing nanobodies even makes it possible to crystallize GPCRs in complex with low-affinity ligands, what was previously only possible with high-affinity ligands (Ring et al, 2013).…”

Section: Single-domain Antibodies As Therapeutics and Tools In Gpcr Rmentioning

confidence: 99%

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Antibodies Targeting Chemokine Receptors CXCR4 and ACKR3

Bobkov

Arimont

Zarca

et al. 2019

Molecular Pharmacology

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Dysregulation of the chemokine system is implicated in a number of autoimmune and inflammatory diseases, as well as cancer. Modulation of chemokine receptor function is a very promising approach for therapeutic intervention. Despite interest from academic groups and pharmaceutical companies, there are currently few approved medicines targeting chemokine receptors. Monoclonal antibodies (mAbs) and antibody-based molecules have been successfully applied in the clinical therapy of cancer and represent a potential new class of therapeutics targeting chemokine receptors belonging to the class of G protein-coupled receptors (GPCRs). Besides conventional mAbs, single-domain antibodies and antibody scaffolds are also gaining attention as promising therapeutics. In this review, we provide an extensive overview of mAbs, singledomain antibodies, and other antibody fragments targeting CXCR4 and ACKR3, formerly referred to as CXCR7. We discuss their unique properties and advantages over smallmolecule compounds, and also refer to the molecules in preclinical and clinical development. We focus on singledomain antibodies and scaffolds and their utilization in GPCR research. Additionally, structural analysis of antibody binding to CXCR4 is discussed. SIGNIFICANCE STATEMENT Modulating the function of GPCRs, and particularly chemokine receptors, draws high interest. A comprehensive review is provided for monoclonal antibodies, antibody fragments, and variants directed at CXCR4 and ACKR3. Their advantageous functional properties, versatile applications as research tools, and use in the clinic are discussed.

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Section: Targeting Cxcr4 and Ackr3 With Antibodiesmentioning

confidence: 99%

Section: Single-domain Antibodies As Therapeutics and Tools In Gpcr Rmentioning

confidence: 99%

Antibodies Targeting Chemokine Receptors CXCR4 and ACKR3

Bobkov

Arimont

Zarca

et al. 2019

Molecular Pharmacology

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“…47 An innovative technology invented by Roche to produce BsAbs is known as the KIH/CrossMAb technology. [48][49] It is described an option to essentially impose correct light chain association when the "knobs-into-holes" approach promotes the combination of bispecific IgG-like antibodies. Besides the initial CH1-CL domain exchange, the VL-VH domain exchange can be enabled by the exchange of charged amino acids.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Monoclonal Antibodies: Structure, Nomenclature and Current Approved Product Review

Xia¹

2019

JAH

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“…As it has been shown previously, additional advantages of BsAbs are that drug resistance and severe adverse effects were much reduced. 5,6 So far, three BsAbs (catumaxomab [anti-EpCAM Â CD3] in 2009, 7 blinatumomab [anti-CD19 Â CD3] in 2014, 8 and emicizumab [anti-Factor IXa Â Factor X] in 2017, 9 have been approved for therapeutic use. The wave of next-generation "bispecific or multispecific antibodies" has arrived.…”

Section: Introductionmentioning

confidence: 99%

Construction of Novel Bispecific Single-Domain Antibodies (BiSdAbs) with Potent Antiangiogenic Activities

Liu

Sun

et al. 2020

Pharmaceutical Fronts

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AbstractThe development of bispecific antibodies (BsAbs) has had a profound impact on cancer immunotherapy. Single-domain antibodies (SdAbs) could offer advantages over other antibody formats for the generation of a BsAbs, such as small size (∼12–15 kDa), with high affinity and specificity, superior accessibility, and high yield expression in bacteria. In this study, VEGFR2 and CD16 were chosen as the targets to construct BsAbs. As the rationale, VEGFR2 is critical for tumor-associated angiogenesis, and CD16 expressed on natural killer cells is an important target on immune cells. Humanized anti-VEGFR2 SdAb 3VGR19 and anti-CD16 SdAb C21 were combined to construct several bispecific SdAbs (BiSdAbs). The biochemical properties of the BiSdAbs were characterized. They retained the high affinity for both targets, binding selectivity, and antiangiogenic activity such as inhibition of cell proliferation, migration, endothelial tube formation, angiogenesis, and cytotoxicity to cancer cells in vitro, indicating that BiSdAbs could be a potential alternative for cancer therapy.

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Therapeutic bispecific antibody formats: a patent applications review (1994-2017)

Cited by 45 publications

References 91 publications

Antibodies Targeting Chemokine Receptors CXCR4 and ACKR3

Antibodies Targeting Chemokine Receptors CXCR4 and ACKR3

Therapeutic Monoclonal Antibodies: Structure, Nomenclature and Current Approved Product Review

Construction of Novel Bispecific Single-Domain Antibodies (BiSdAbs) with Potent Antiangiogenic Activities

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