Bispecific antibodies

Coloma, 1997, Design and production of novel tetravalent bispecific antibodies, Nat. Biotechnol., 15, 159, 10.1038/nbt0297-159

Kontermann, 2012, Dual targeting strategies with bispecific antibodies, mAbs, 4, 182, 10.4161/mabs.4.2.19000

Metz, 2011, Bispecific digoxigenin-binding antibodies for targeted payload delivery, Proc. Natl. Acad. Sci. U. S. A., 108, 8194, 10.1073/pnas.1018565108

Schanzer, 2011, Development of tetravalent, bispecific CCR5 antibodies with antiviral activity against CCR5 monoclonal antibody-resistant HIV-1 strains, Antimicrob. Agents Chemother., 55, 2369, 10.1128/AAC.00215-10

Croasdale, 2012, Development of tetravalent IgG1 dual targeting IGF-1R-EGFR antibodies with potent tumor inhibition, Arch. Biochem. Biophys., 526, 206, 10.1016/j.abb.2012.03.016

Castoldi, 2012, Molecular characterization of novel trispecific ErbB-cMet-IGF1R antibodies and their antigen-binding properties, Protein Eng. Des. Sel., 25, 551, 10.1093/protein/gzs048

Kou, 2010, A bispecific antibody effectively inhibits tumor growth and metastasis by simultaneous blocking vascular endothelial growth factor A and osteopontin, Cancer Lett., 299, 130, 10.1016/j.canlet.2010.08.011

Kontermann, 2010, Alternative antibody formats, Curr. Opin. Mol. Ther., 12, 176

Metz, 2012, Bispecific antibody derivatives with restricted binding functionalities that are activated by proteolytic processing, Protein Eng. Des. Sel., 25, 571, 10.1093/protein/gzs064

Schaefer, 2011, A two-in-one antibody against HER3 and EGFR has superior inhibitory activity compared with monospecific antibodies, Cancer Cell, 20, 472, 10.1016/j.ccr.2011.09.003

Bostrom, 2009, Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site, Science, 323, 1610, 10.1126/science.1165480

Ridgway, 1996, ‘Knobs-into-holes’ engineering of antibody CH3 domains for heavy chain heterodimerization, Protein Eng., 9, 617, 10.1093/protein/9.7.617

Davis, 2010, 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, Protein Eng. Des. Sel., 23, 195, 10.1093/protein/gzp094

Merchant, 1998, An efficient route to human bispecific IgG, Nat. Biotechnol., 16, 677, 10.1038/nbt0798-677

Spiess, 2013, Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies, Nat. Biotechnol., 31, 753, 10.1038/nbt.2621

Schaefer, 2011, Immunoglobulin domain crossover as a generic approach for the production of bispecific IgG antibodies, Proc. Natl. Acad. Sci. U. S. A., 108, 11187, 10.1073/pnas.1019002108

Klein, 2012, Progress in overcoming the chain association issue in bispecific heterodimeric IgG antibodies, mAbs, 4, 653, 10.4161/mabs.21379

Müller, 2007, Recombinant bispecific antibodies for cellular cancer immunotherapy, Curr. Opin. Mol. Ther., 9, 319

Kontermann, 2009, Strategies to extend plasma half-lives of recombinant antibodies, BioDrugs, 23, 93, 10.2165/00063030-200923020-00003

Wu, 2007, Simultaneous targeting of multiple disease mediators by a dual-variable-domain immunoglobulin, Nat. Biotechnol., 25, 1290, 10.1038/nbt1345

Von Kreutenstein, 2013, Improving biophysical properties of a bispecific antibody scaffold to aid developability: quality by molecular design, mAbs, 5, 646, 10.4161/mabs.25632

Gunasekaran, 2010, Enhancing antibody Fc heterodimer formation through electrostatic steering effects: applications to bispecific molecules and monovalent antibodies, J. Biol. Chem., 285, 19637, 10.1074/jbc.M110.117382

Lewis, 2014, Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface, Nat. Biotechnol., 32, 191, 10.1038/nbt.2797

Hayden, 1994, Single-chain mono- and bispecific antibody derivatives with novel biological properties and antitumour activity from a COS cell transient expression system, Ther. Immunol., 1, 3

Holliger, 1994, ‘Diabodies’: small bivalent and bispecific antibody fragments, Proc. Natl. Acad. Sci. U. S. A., 90, 6444, 10.1073/pnas.90.14.6444

Brüsselbach, 1999, Enzyme recruitment and tumor cell killing in vitro by a secreted bispecific single-chain diabody, Tumor Target., 4, 115

Kipriyanov, 1999, Bispecific tandem diabody for tumor therapy with improved antigen binding and pharmacokinetics, J. Mol. Biol., 293, 41, 10.1006/jmbi.1999.3156

Johnson, 2010, Effector cell recruitment with novel Fv-based dual-affinity re-targeting protein leads to potent tumor cytolysis and in vivo B cell depletion, J. Mol. Biol., 399, 436, 10.1016/j.jmb.2010.04.001

Kontermann, 2011, Strategies for extended serum half-life of protein therapeutics, Curr. Opin. Biotechnol., 22, 868, 10.1016/j.copbio.2011.06.012

Müller, 2007, Improved pharmacokinetics of recombinant bispecific antibody molecules by fusion to human serum albumin, J. Biol. Chem., 282, 12650, 10.1074/jbc.M700820200

McDonagh, 2012, Antitumor activity of a novel bispecific antibody that targets the ErbB2/ErbB3 oncogenic unit and inhibits heregulin-induced activation of ErbB3, Mol. Cancer Ther., 11, 582, 10.1158/1535-7163.MCT-11-0820

Rossi, 2006, Stably tethered multifunctional structures of defined composition made by the dock and lock method for use in cancer targeting, Proc. Natl. Acad. Sci. U. S. A., 103, 6841, 10.1073/pnas.0600982103

Rossi, 2012, The dock-and-lock method combines recombinant engineering with site-specific covalent conjugation to generate multifunctional structures, Bioconjug. Chem., 23, 309, 10.1021/bc2004999

Heiss, 2005, Immunotherapy of malignant ascites with trifunctional antibodies, Int. J. Cancer., 117, 435, 10.1002/ijc.21165

Zeidler, 2000, The Fc-region of a new class of intact bispecific antibody mediates activation of accessory cells and NK cells and induces direct phagocytosis of tumour cells, Br. J. Cancer, 83, 261, 10.1054/bjoc.2000.1237

Lindhofer, 1995, Preferential species-restricted heavy/light chain pairing in rat/mouse quadromas. Implications for a single-step purification of bispecific antibodies, J. Immunol., 155, 219, 10.4049/jimmunol.155.1.219

Jäger, 2009, The trifunctional antibody ertumaxomab destroys tumor cells that express low levels of human epidermal growth factor receptor 2, Cancer Res., 69, 4270, 10.1158/0008-5472.CAN-08-2861

Stanglmaier, 2008, Bi20 (FBTA05), a novel trifunctional bispecific antibody (anti-CD20×anti-CD3), mediates efficient killing of B cell lymphoma cells even with very low CD20 expression levels, Int. J. Cancer, 123, 1181, 10.1002/ijc.23626

Ruf, 2004, Two new trifunctional antibodies for the therapy of human malignant melanoma, Int. J. Cancer, 108, 725, 10.1002/ijc.11630

Ruf, 2001, Induction of a long-lasting antitumor immunity by a trifunctional bispecific antibody, Blood, 98, 2526, 10.1182/blood.V98.8.2526

Burges, 2007, Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM×anti-CD3 antibody: a phase I/II study, Clin. Cancer Res., 13, 3899, 10.1158/1078-0432.CCR-06-2769

Buhmann, 2009, Immunotherapy of recurrent B cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti-CD3×anti-CD20 antibody and donor lymphocyte infusion, Bone Marrow Transplant., 43, 383, 10.1038/bmt.2008.323

Kufer, 2004, A revival of bispecific antibodies, Trends Biotechnol., 22, 238, 10.1016/j.tibtech.2004.03.006

Baeuerle, 2009, BiTE: teaching antibodies to engage T cells for cancer therapy, Curr. Opin. Mol. Ther., 11, 22

Wolf, 2005, BiTEs: bispecific antibody constructs with unique anti-tumor activity, Drug Discov. Today, 10, 1237, 10.1016/S1359-6446(05)03554-3

Baeuerle, 2009, Bispecific T cell engaging antibodies for cancer therapy, Cancer Res., 69, 4941, 10.1158/0008-5472.CAN-09-0547

Mack, 1995, A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity, Proc. Natl. Acad. Sci. U. S. A., 92, 7021, 10.1073/pnas.92.15.7021

Dreier, 2002, Extremely potent, rapid and costimulation-independent cytotoxic T cell response against lymphoma cells catalysed by a single-chain bispecific antibody, Int. J. Cancer, 100, 690, 10.1002/ijc.10557

Hoffmann, 2005, Serial killing of tumor cells by cytotoxic T cells redirected with a CD19-/CD3-bispecific single-chain antibody construct, Int. J. Cancer, 115, 98, 10.1002/ijc.20908

Haas, 2009, Mode of cytotoxic action of T cell-engaging BiTE antibody MT110, Immunobiology, 214, 441, 10.1016/j.imbio.2008.11.014

Dreier, 2003, T cell costimulus-independent and very efficacious inhibition of tumor growth in mice bearing subcutaneous or leukemic human B cell lymphoma xenografts by a CD19-/CD3-bispecific single-chain antibody construct, J. Immunol., 170, 4397, 10.4049/jimmunol.170.8.4397

Schlereth, 2005, Eradication of tumors from a human colon cancer cell line and from ovarian cancer metastases in immunodeficient mice by a single-chain Ep-CAM-/CD3-bispecific antibody construct, Cancer Res., 65, 2882, 10.1158/0008-5472.CAN-04-2637

Topp, 2014, Phase II trial of the anti-CD19 bispecific T cell-engager Blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia, J. Clin. Oncol., 10.1200/JCO.2014.56.3247

Löffler, 2003, Efficient elimination of chronic lymphocytic leukaemia B cells by autologous T cells with a bispecific anti-CD19/anti-CD3 single-chain antibody construct, Leukemia, 17, 900, 10.1038/sj.leu.2402890

Bargou, 2008, Tumor regression in cancer patients by very low doses of a T cell-engaging antibody, Science, 321, 974, 10.1126/science.1158545

Moore, 2011, Application of dual affinity retargeting molecules to achieve optimal redirected T cell killing of B cell lymphoma, Blood, 117, 4542, 10.1182/blood-2010-09-306449

McAleese, 2012, RECRUIT-TandAbs®: harnessing the immune system to kill cancer cells, Future Oncol., 8, 687, 10.2217/fon.12.54

Cochlovius, 2000, Cure of Burkitt's lymphoma in severe combined immunodeficiency mice by T cells, tetravalent CD3×CD19 tandem diabody, and CD28 costimulation, Cancer Res., 60, 4336

Yarden, 2001, Untangling the ErbB signalling network, Nat. Rev. Mol. Cell Biol., 2, 127, 10.1038/35052073

Slamon, 1987, Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene, Science, 235, 177, 10.1126/science.3798106

Holbro, 2003, The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation, Proc. Natl. Acad. Sci. U. S. A., 100, 8933, 10.1073/pnas.1537685100

Robinson, 2008, Targeting ErbB2 and ErbB3 with a bispecific single-chain Fv enhances targeting selectivity and induces a therapeutic effect in vitro, Br. J. Cancer, 99, 1415, 10.1038/sj.bjc.6604700

Fitzgerald, 2014, MM-141, an IGF-IR- and ErbB3-directed bispecific antibody, overcomes network adaptations that limit activity of IGF-IR inhibitors, Mol. Cancer Ther., 13, 410, 10.1158/1535-7163.MCT-13-0255

Gong, 2009, High expression levels of total IGF-1R and sensitivity of NSCLC cells in vitro to an anti-IGF-1R antibody (R1507), PLoS ONE, 4, e7273, 10.1371/journal.pone.0007273

Kurzrock, 2010, A phase I study of weekly R1507, a human monoclonal antibody insulin-like growth factor-I receptor antagonist, in patients with advanced solid tumors, Clin. Cancer Res., 16, 2458, 10.1158/1078-0432.CCR-09-3220

Chen, 2012, Human monoclonal antibodies targeting nonoverlapping epitopes on insulin-like growth factor II as a novel type of candidate cancer therapeutics, Mol. Cancer Ther., 11, 1400, 10.1158/1535-7163.MCT-12-0172

Garber, 2014, Bispecific antibodies rise again, Nat. Rev. Drug Discov., 13, 799, 10.1038/nrd4478

Reichert, 2012, The future of antibodies as cancer drugs, Drug Discov. Today, 17, 954, 10.1016/j.drudis.2012.04.006

Wu, 2009, Molecular construction and optimization of anti-human IL-1α/β dual variable domain immunoglobulin (DVD-Ig™) molecules, mAbs, 1, 339, 10.4161/mabs.1.4.8755

Moses, 2013

Ferrara, 2003, The biology of VEGF and its receptors, Nat. Med., 9, 669, 10.1038/nm0603-669

Kerbel, 2008, Tumor angiogenesis, N. Engl. J. Med., 358, 2039, 10.1056/NEJMra0706596

Kienast, 2013, Ang-2-VEGF-A CrossMab, a novel bispecific human IgG1 antibody blocking VEGF-A and Ang-2 functions simultaneously, mediates potent antitumor, antiangiogenic, and antimetastatic efficacy, Clin. Cancer Res., 19, 6730, 10.1158/1078-0432.CCR-13-0081

Weidle, 2014, Tumor-antigen-binding bispecific antibodies for cancer treatment, Semin. Oncol., 41, 653, 10.1053/j.seminoncol.2014.08.004

Gemmy, 2014, Dual inhibition of angiopoietin-2 and vascular endothelial growth factor-A with Crossmab RG7716 suppressed laser-induced choroidal neovascularization in a non-human primate model, Invest. Ophthalmol. Vis. Sci., 55

Rao, 2012, Generation of a tetravalent bispecific antibody against IL4 and IL13 for the treatment of idiopathic pulmonary fibrosis, mAbs, 4, 14

Mabry, 2010, Engineering of stable bispecific antibodies targeting IL-17A and IL-23, Protein Eng. Des. Sel., 23, 115, 10.1093/protein/gzp073

McBride, 2006, Bispecific antibody pretargeting PET (immunoPET) with an 124I-labeled hapten-peptide, J. Nucl. Med., 47, 1678

Kitazawa, 2012, A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model, Nat. Med., 18, 1570, 10.1038/nm.2942

Sampei, 2013, Identification and multidimensional optimization of an asymmetric bispecific IgG antibody mimicking the function of factor VIII cofactor activity, PLOS ONE, 8, e57479, 10.1371/journal.pone.0057479

Muto, 2014, Anti-factor IXa/X bispecific antibody (ACE910): hemosatic potency against ongoing bleeds in a hemophilia A model and the possibility of routine supplementation, J. Thromb. Haemost., 12, 206, 10.1111/jth.12474

Muto, 2014, Anti-factor IXa/X bispecific antibody ACE910 prevents joint bleeds in a long-term primate model of acquired hemophilia A, Blood, 124, 3165, 10.1182/blood-2014-07-585737

Xu, 2015, Production of bispecific antibodies in ‘knobs-into-holes’ using a cell-free expression system, mAbs, 7, 231, 10.4161/19420862.2015.989013