Bispecific antibodies in cancer immunotherapy

References

• Apperley JF. Chronic myeloid leukaemia. Lancet 2015; 385:1447-59; PMID:25484026; http://dx.doi.org/10.1016/S0140-6736(13)62120-0
   PubMed Web of Science ®Google Scholar
• Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science 2013; 342:1432-3; PMID:24357284; http://dx.doi.org/10.1126/science.342.6165.1432
   PubMed Web of Science ®Google Scholar
• Le Mercier I, Lines JL, Noelle RJ. Beyond CTLA-4 and PD-1, the generation Z of negative checkpoint regulators. Front Immunol 2015; 6:418; PMID:26347741; http://dx.doi.org/10.3389/fimmu.2015.00418
   PubMed Web of Science ®Google Scholar
• Yang Y. Cancer immunotherapy: harnessing the immune system to battle cancer. J Clin Invest 2015; 125:3335-7; PMID:26325031; http://dx.doi.org/10.1172/JCI83871
   PubMed Web of Science ®Google Scholar
• Kontermann R. Dual targeting strategies with bispecific antibodies. MAbs 2012; 4:182-97; PMID:22453100; http://dx.doi.org/10.4161/mabs.4.2.19000
   PubMed Web of Science ®Google Scholar
• Kontermann RE, Brinkmann U. Bispecific antibodies. Drug Discov Today 2015; 20:838-47; PMID:25728220; http://dx.doi.org/10.1016/j.drudis.2015.02.008
   PubMed Web of Science ®Google Scholar
• Heiss MM. The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: results of a prospective randomized Phase II/III trial. Int J Cancer 2010; 127:2209-21; PMID:20473913; http://dx.doi.org/10.1002/ijc.25423
   PubMed Web of Science ®Google Scholar
• Przepiorka D, Ko CW, Deisseroth A, Yancey CL, Candau-Chacon R, Chiu HJ, Gehrke BJ, Gomez-Broughton C, Kane RC, Kirshner S, et al. FDA Approval: Blinatumomab. Clin Cancer Res 2015; 21:4035-9; PMID:26374073; http://dx.doi.org/10.1158/1078-0432.CCR-15-0612
   PubMed Web of Science ®Google Scholar
• Newman MJ, Benani DJ. A review of blinatumomab, a novel immunotherapy. J Oncol Pharm Pract 2015; PMID:26607163
   PubMed Web of Science ®Google Scholar
• Staerz UD, Kanagawa O, Bevan MJ. Hybrid antibodies can target sites for attack by T cells. Nature 1985; 314:628-31; PMID:2859527; http://dx.doi.org/10.1038/314628a0
   PubMed Web of Science ®Google Scholar
• Nisonoff A, Rivers MM. Recombination of a mixture of univalent antibody fragments of different specificity. Arch Biochem Biophys 1961; 93:460-2; PMID:13729244; http://dx.doi.org/10.1016/0003-9861(61)90296-X
   PubMed Web of Science ®Google Scholar
• Yankelevich M, Kondadasula SV, Thakur A, Buck S, Cheung NK, Lum LG. Anti-CD3 x anti-GD2 bispecific antibody redirects T-cell cytolytic activity to neuroblastoma targets. Pediatr Blood Cancer 2012; 59:1198-205; PMID:22707078; http://dx.doi.org/10.1002/pbc.24237
   PubMed Web of Science ®Google Scholar
• Sen M, Wankowski DM, Garlie NK, Siebenlist RE, Van Epps D, LeFever AV, Lum LG. Use of anti-CD3 x anti-HER2/neu bispecific antibody for redirecting cytotoxicity of activated T cells toward HER2/neu+ tumors. J Hematother Stem Cell Res 2001; 10:247-60; PMID:11359672; http://dx.doi.org/10.1089/15258160151134944
   PubMedGoogle Scholar
• Weiner GJ. Building better monoclonal antibody-based therapeutics. Nature reviews Cancer 2015; 15:361-70; PMID:25998715; http://dx.doi.org/10.1038/nrc3930
   PubMed Web of Science ®Google Scholar
• Batlevi CL, Matsuki E, Brentjens RJ, Younes A. Novel immunotherapies in lymphoid malignancies. Nat Rev Clin Oncol 2016; 13:25-40; PMID:26525683; http://dx.doi.org/10.1038/nrclinonc.2015.187
   PubMed Web of Science ®Google Scholar
• Byrne H, Conroy PJ, Whisstock JC, O'Kennedy RJ. A tale of two specificities: bispecific antibodies for therapeutic and diagnostic applications. Trends Biotechnol 2013; 31:621-32; PMID:24094861; http://dx.doi.org/10.1016/j.tibtech.2013.08.007
   PubMed Web of Science ®Google Scholar
• Chelius D, Ruf P, Gruber P, Ploscher M, Liedtke R, Gansberger E, Hess J, Wasiliu M, Lindhofer H. Structural and functional characterization of the trifunctional antibody catumaxomab. MAbs 2010; 2:309-19; PMID:20418662; http://dx.doi.org/10.4161/mabs.2.3.11791
   PubMed Web of Science ®Google Scholar
• Berek JS, Edwards RP, Parker LP, DeMars LR, Herzog TJ, Lentz SS, Morris RT, Akerley WL, Holloway RW, Method MW, et al. Catumaxomab for the treatment of malignant ascites in patients with chemotherapy-refractory ovarian cancer: a phase II study. Int J Gynecol Cancer 2014; 24:1583-9; PMID:25254563; http://dx.doi.org/10.1097/IGC.0000000000000286
   PubMed Web of Science ®Google Scholar
• Mau-Sorensen M, Dittrich C, Dienstmann R, Lassen U, Buchler W, Martinius H, Tabernero J. A phase I trial of intravenous catumaxomab: a bispecific monoclonal antibody targeting EpCAM and the T cell coreceptor CD3. Cancer Chemother Pharmacol 2015; 75:1065-73; PMID:25814216; http://dx.doi.org/10.1007/s00280-015-2728-5
   PubMed Web of Science ®Google Scholar
• Frankel SR, Baeuerle PA. Targeting T cells to tumor cells using bispecific antibodies. Curr Opin Chem Biol 2013; 17:385-92; PMID:23623807; http://dx.doi.org/10.1016/j.cbpa.2013.03.029
   PubMed Web of Science ®Google Scholar
• Cochlovius B. Cure of Burkitt's lymphoma in severe combined immunodeficiency mice by T cells, tetravalent CD3 x CD19 tandem diabody, and CD28 costimulation. Cancer Res 2000; 60:4336-41; PMID:10969772
   PubMed Web of Science ®Google Scholar
• Oates J, Hassan NJ, Jakobsen BK. ImmTACs for targeted cancer therapy: Why, what, how, and which. Mol Immunol 2015; 67:67-74; PMID:25708206; http://dx.doi.org/10.1016/j.molimm.2015.01.024
   PubMed Web of Science ®Google Scholar
• Oates J, Jakobsen BK. ImmTACs: Novel bi-specific agents for targeted cancer therapy. Oncoimmunology 2013; 2:e22891; PMID:23525668; http://dx.doi.org/10.4161/onci.22891
   PubMed Web of Science ®Google Scholar
• Bostrom J, Yu SF, Kan D, Appleton BA, Lee CV, Billeci K, Man W, Peale F, Ross S, Wiesmann C, et al. Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site. Science 2009; 323:1610-4; PMID:19299620; http://dx.doi.org/10.1126/science.1165480
   PubMed Web of Science ®Google Scholar
• Orcutt KD, Ackerman ME, Cieslewicz M, Quiroz E, Slusarczyk AL, Frangioni JV, Wittrup KD. A modular IgG-scFv bispecific antibody topology. Protein Eng Des Sel 2010; 23:221-8; PMID:20019028; http://dx.doi.org/10.1093/protein/gzp077
   PubMed Web of Science ®Google Scholar
• Schaefer W, Regula JT, Bahner M, Schanzer J, Croasdale R, Durr H, Gassner C, Georges G, Kettenberger H, Imhof-Jung S, et al. Immunoglobulin domain crossover as a generic approach for the production of bispecific IgG antibodies. Proc Natl Acad Sci U S A 2011; 108:11187-92; PMID:21690412; http://dx.doi.org/10.1073/pnas.1019002108
   PubMed Web of Science ®Google Scholar
• Rossi EA, Goldenberg DM, Cardillo TM, McBride WJ, Sharkey RM, Chang CH. 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 2006; 103:6841-6; PMID:16636283; http://dx.doi.org/10.1073/pnas.0600982103
   PubMed Web of Science ®Google Scholar
• Wu C, Ying H, Grinnell C, Bryant S, Miller R, Clabbers A, Bose S, McCarthy D, Zhu RR, Santora L, et al. Simultaneous targeting of multiple disease mediators by a dual-variable-domain immunoglobulin. Nat Biotechnol 2007; 25:1290-7; PMID:17934452; http://dx.doi.org/10.1038/nbt1345
   PubMed Web of Science ®Google Scholar
• Gu J, Ghayur T. Generation of dual-variable-domain immunoglobulin molecules for dual-specific targeting. Methods Enzymol 2012; 502:25-41; PMID:22208980; http://dx.doi.org/10.1016/B978-0-12-416039-2.00002-1
   PubMed Web of Science ®Google Scholar
• Jakob CG, Edalji R, Judge RA, DiGiammarino E, Li Y, Gu J, Ghayur T. Structure reveals function of the dual variable domain immunoglobulin (DVD-Ig) molecule. MAbs 2013; 5:358-63; PMID:23549062; http://dx.doi.org/10.4161/mabs.23977
   PubMed Web of Science ®Google Scholar
• Els Conrath K, Lauwereys M, Wyns L, Muyldermans S. Camel single-domain antibodies as modular building units in bispecific and bivalent antibody constructs. J Biol Chem 2001; 276:7346-50; PMID:11053416; http://dx.doi.org/10.1074/jbc.M007734200
   PubMed Web of Science ®Google Scholar
• Lazar GA. Engineered antibody Fc variants with enhanced effector function. Proc Natl Acad Sci USA 2006; 103:4005-10
   PubMed Web of Science ®Google Scholar
• Seimetz D, Lindhofer H, Bokemeyer C. Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy. Cancer Treat Rev 2010; 36:458-67; PMID:20347527; http://dx.doi.org/10.1016/j.ctrv.2010.03.001
   PubMed Web of Science ®Google Scholar
• Zeidler R, Mysliwietz J, Csanady M, Walz A, Ziegler I, Schmitt B, Wollenberg B, Lindhofer H. 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 2000; 83:261-6; PMID:10901380; http://dx.doi.org/10.1054/bjoc.2000.1237
   PubMed Web of Science ®Google Scholar
• Stanglmaier M, Faltin M, Ruf P, Bodenhausen A, Schroder P, Lindhofer H. Bi20 (fBTA05), a novel trifunctional bispecific antibody (anti-CD20 x anti-CD3), mediates efficient killing of B-cell lymphoma cells even with very low CD20 expression levels. Int J Cancer 2008; 123:1181-9; PMID:18546289; http://dx.doi.org/10.1002/ijc.23626
   PubMed Web of Science ®Google Scholar
• Jager M, Schoberth A, Ruf P, Hess J, Lindhofer H. The trifunctional antibody ertumaxomab destroys tumor cells that express low levels of human epidermal growth factor receptor 2. Cancer Res 2009; 69:4270-6; PMID:19435924; http://dx.doi.org/10.1158/0008-5472.CAN-08-2861
   PubMed Web of Science ®Google Scholar
• Buhmann R, Michael S, Juergen H, Horst L, Peschel C, Kolb HJ. Immunotherapy with FBTA05 (Bi20), a trifunctional bispecific anti-CD3 x anti-CD20 antibody and donor lymphocyte infusion (DLI) in relapsed or refractory B-cell lymphoma after allogeneic stem cell transplantation: study protocol of an investigator-driven, open-label, non-randomized, uncontrolled, dose-escalating Phase I/II-trial. J Transl Med 2013; 11:160; PMID:23815981; http://dx.doi.org/10.1186/1479-5876-11-160
   PubMed Web of Science ®Google Scholar
• Milstein C, Cuello AC. Hybrid hybridomas and their use in immunohistochemistry. Nature 1983; 305:537-40; PMID:6137772; http://dx.doi.org/10.1038/305537a0
   PubMed Web of Science ®Google Scholar
• Suresh MR, Cuello AC, Milstein C. Advantages of bispecific hybridomas in one-step immunocytochemistry and immunoassays. Proc Natl Acad Sci U S A 1986; 83:7989-93; PMID:2429324; http://dx.doi.org/10.1073/pnas.83.20.7989
   PubMed Web of Science ®Google Scholar
• Atwell S, Ridgway JB, Wells JA, Carter P. Stable heterodimers from remodeling the domain interface of a homodimer using a phage display library. J Mol Biol 1997; 270:26-35; PMID:9231898; http://dx.doi.org/10.1006/jmbi.1997.1116
   PubMed Web of Science ®Google Scholar
• Ridgway JB, Presta LG, Carter P. 'Knobs-into-holes' engineering of antibody CH3 domains for heavy chain heterodimerization. Protein Eng 1996; 9:617-21; PMID:8844834; http://dx.doi.org/10.1093/protein/9.7.617
   PubMedGoogle Scholar
• Gunasekaran K, Pentony M, Shen M, Garrett L, Forte C, Woodward A, Ng SB, Born T, Retter M, Manchulenko K, et al. Enhancing antibody Fc heterodimer formation through electrostatic steering effects: applications to bispecific molecules and monovalent IgG. J Biol Chem 2010; 285:19637-46; PMID:20400508; http://dx.doi.org/10.1074/jbc.M110.117382
   PubMed Web of Science ®Google Scholar
• Strop P, Ho WH, Boustany LM, Abdiche YN, Lindquist KC, Farias SE, Rickert M, Appah CT, Pascua E, Radcliffe T, et al. Generating bispecific human IgG1 and IgG2 antibodies from any antibody pair. J Mol Biol 2012; 420:204-19; PMID:22543237; http://dx.doi.org/10.1016/j.jmb.2012.04.020
   PubMed Web of Science ®Google Scholar
• Von Kreudenstein TS, Escobar-Carbrera E, Lario PI, D'Angelo I, Brault K, Kelly J, Durocher Y, Baardsnes J, Woods RJ, Xie MH, et al. Improving biophysical properties of a bispecific antibody scaffold to aid developability: Quality by molecular design. mAbs 2013; 5:646-54; PMID:23924797
   PubMed Web of Science ®Google Scholar
• Davis JH, Aperlo C, Li Y, Kurosawa E, Lan Y, Lo KM, Huston JS. 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 2010; 23:195-202; PMID:20299542; http://dx.doi.org/10.1093/protein/gzp094
   PubMed Web of Science ®Google Scholar
• Spiess C, Bevers J, 3rd, Jackman J, Chiang N, Nakamura G, Dillon M, Liu H, Molina P, Elliott JM, Shatz W, et al. Development of a human IgG4 bispecific antibody for dual targeting of interleukin-4 (IL-4) and interleukin-13 (IL-13) cytokines. J Biol Chem 2013; 288:26583-93; PMID:23880771; http://dx.doi.org/10.1074/jbc.M113.480483
   PubMed Web of Science ®Google Scholar
• Merchant AM, Zhu Z, Yuan JQ, Goddard A, Adams CW, Presta LG, Carter P. An efficient route to human bispecific IgG. Nat Biotechnol 1998; 16:677-81; PMID:9661204; http://dx.doi.org/10.1038/nbt0798-677
   PubMed Web of Science ®Google Scholar
• Dhimolea E, Reichert JM. World Bispecific Antibody Summit, September 27-28, 2011, Boston, MA. MAbs 2012; 4:4-13
   Google Scholar
• Spiess C, Merchant M, Huang A, Zheng Z, Yang NY, Peng J, Ellerman D, Shatz W, Reilly D, Yansura DG, et al. Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies. Nat Biotechnol 2013; PMID:23831709
   PubMed Web of Science ®Google Scholar
• Jackman J, Chen Y, Huang A, Moffat B, Scheer JM, Leong SR, Lee WP, Zhang J, Sharma N, Lu Y, et al. Development of a two-part strategy to identify a therapeutic human bispecific antibody that inhibits IgE receptor signaling. J Biol Chem 2010; 285:20850-9; PMID:20444694; http://dx.doi.org/10.1074/jbc.M110.113910
   PubMed Web of Science ®Google Scholar
• Spiess C, Zhai Q, Carter PJ. Alternative molecular formats and therapeutic applications for bispecific antibodies. Mol Immunol 2015; 67:95-106; PMID:25637431; http://dx.doi.org/10.1016/j.molimm.2015.01.003
   PubMed Web of Science ®Google Scholar
• LaFleur DW, Abramyan D, Kanakaraj P, Smith RG, Shah RR, Wang G, Yao XT, Kankanala S, Boyd E, Zaritskaya L, et al. Monoclonal antibody therapeutics with up to five specificities: functional enhancement through fusion of target-specific peptides. MAbs 2013; 5:208-18; PMID:23575268; http://dx.doi.org/10.4161/mabs.23043
   PubMed Web of Science ®Google Scholar
• Fenn S, Schiller CB, Griese JJ, Duerr H, Imhof-Jung S, Gassner C, Moelleken J, Regula JT, Schaefer W, Thomas M, et al. Crystal structure of an anti-Ang2 CrossFab demonstrates complete structural and functional integrity of the variable domain. PLoS One 2013; 8:e61953; PMID:23613981
   PubMed Web of Science ®Google Scholar
• Lewis SM, Wu X, Pustilnik A, Sereno A, Huang F, Rick HL, Guntas G, Leaver-Fay A, Smith EM, Ho C, et al. Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface. Nat Biotechnol 2014; 32:191-8; PMID:24463572; http://dx.doi.org/10.1038/nbt.2797
   PubMed Web of Science ®Google Scholar
• Schaefer G, Haber L, Crocker LM, Shia S, Shao L, Dowbenko D, Totpal K, Wong A, Lee CV, Stawicki S, et al. A two-in-one antibody against HER3 and EGFR has superior inhibitory activity compared with monospecific antibodies. Cancer Cell 2011; 20:472-86; PMID:22014573; http://dx.doi.org/10.1016/j.ccr.2011.09.003
   PubMed Web of Science ®Google Scholar
• Eigenbrot C, Fuh G. Two-in-One antibodies with dual action Fabs. Curr Opin Chem Biol 2013; 17:400-5; PMID:23683347; http://dx.doi.org/10.1016/j.cbpa.2013.04.015
   PubMed Web of Science ®Google Scholar
• Hu S, Fu W, Xu W, Yang Y, Cruz M, Berezov SD, Jorissen D, Takeda H, Zhu W. Four-in-one antibodies have superior cancer inhibitory activity against EGFR, HER2, HER3, and VEGF through disruption of HER/MET crosstalk. Cancer Res 2015; 75:159-70; PMID:25371409; http://dx.doi.org/10.1158/0008-5472.CAN-14-1670
   PubMed Web of Science ®Google Scholar
• Albrecht H, Denardo GL, Denardo SJ. Monospecific bivalent scFv-SH: effects of linker length and location of an engineered cysteine on production, antigen binding activity and free SH accessibility. J Immunol Methods 2006; 310:100-16; PMID:16499921; http://dx.doi.org/10.1016/j.jim.2005.12.012
   PubMed Web of Science ®Google Scholar
• Holliger P, Prospero T, Winter G. “Diabodies”: small bivalent and bispecific antibody fragments. Proc Natl Acad Sci U S A 1993; 90:6444-8; PMID:8341653
   PubMed Web of Science ®Google Scholar
• Johnson S, Burke S, Huang L, Gorlatov S, Li H, Wang W, Zhang W, Tuaillon N, Rainey J, Barat B, et al. 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 2010; 399:436-49; PMID:20382161; http://dx.doi.org/10.1016/j.jmb.2010.04.001
   PubMed Web of Science ®Google Scholar
• Baeuerle PA, Kufer P, Bargou R. BiTE: Teaching antibodies to engage T-cells for cancer therapy. Curr Opin Mol Ther 2009; 11:22-30; PMID:19169956
   PubMed Web of Science ®Google Scholar
• Baeuerle PA, Reinhardt C. Bispecific T-cell engaging antibodies for cancer therapy. Cancer Res 2009; 69:4941-4; PMID:19509221; http://dx.doi.org/10.1158/0008-5472.CAN-09-0547
   PubMed Web of Science ®Google Scholar
• Hayden MS, Linsley PS, Gayle MA, Bajorath J, Brady WA, Norris NA, Fell HP, Ledbetter JA, Gilliland LK. Single-chain mono- and bispecific antibody derivatives with novel biological properties and antitumour activity from a COS cell transient expression system. Ther Immunol 1994; 1:3-15; PMID:7584477
   PubMedGoogle Scholar
• Muller D, Kontermann RE. Bispecific antibodies for cancer immunotherapy: Current perspectives. Biodrugs 2010; 24:89-98; PMID:20199124; http://dx.doi.org/10.2165/11530960-000000000-00000
   PubMed Web of Science ®Google Scholar
• Kellner C, Bruenke J, Stieglmaier J, Schwemmlein M, Schwenkert M, Singer H, Mentz K, Peipp M, Lang P, Oduncu F, et al. A novel CD19-directed recombinant bispecific antibody derivative with enhanced immune effector functions for human leukemic cells. J Immunother 2008; 31:871-84; PMID:18833000; http://dx.doi.org/10.1097/CJI.0b013e318186c8b4
   PubMed Web of Science ®Google Scholar
• Dreier T, Lorenczewski G, Brandl C, Hoffmann P, Syring U, Hanakam F, Kufer P, Riethmuller G, Bargou R, Baeuerle PA. Extremely potent, rapid and costimulation-independent cytotoxic T-cell response against lymphoma cells catalyzed by a single-chain bispecific antibody. Int J Cancer 2002; 100:690-7; PMID:12209608; http://dx.doi.org/10.1002/ijc.10557
   PubMed Web of Science ®Google Scholar
• Wolf E, Hofmeister R, Kufer P, Schlereth B, Baeuerle PA. BiTEs: bispecific antibody constructs with unique anti-tumor activity. Drug Discov Today 2005; 10:1237-44; PMID:16213416; http://dx.doi.org/10.1016/S1359-6446(05)03554-3
   PubMed Web of Science ®Google Scholar
• Offner S, Hofmeister R, Romaniuk A, Kufer P, Baeuerle PA. Induction of regular cytolytic T cell synapses by bispecific single-chain antibody constructs on MHC class I-negative tumor cells. Mol Immunol 2006; 43:763-71; PMID:16360021; http://dx.doi.org/10.1016/j.molimm.2005.03.007
   PubMed Web of Science ®Google Scholar
• Schlereth B, Quadt C, Dreier T, Kufer P, Lorenczewski G, Prang N, Brandl C, Lippold S, Cobb K, Brasky K, et al. T-cell activation and B-cell depletion in chimpanzees treated with a bispecific anti-CD19/anti-CD3 single-chain antibody construct. Cancer Immunol Immunother 2006; 55:503-14; PMID:16032400; http://dx.doi.org/10.1007/s00262-005-0001-1
   PubMed Web of Science ®Google Scholar
• Bargou R, Leo E, Zugmaier G, Klinger M, Goebeler M, Knop S, Noppeney R, Viardot A, Hess G, Schuler M, et al. Tumor Regression in Cancer Patients by Very Low Doses of a T Cell–Engaging Antibody. Science 2008; 321:974-7; PMID:18703743; http://dx.doi.org/10.1126/science.1158545
   PubMed Web of Science ®Google Scholar
• Haas C, Krinner E, Brischwein K, Hoffmann P, Lutterbuse R, Schlereth B, Kufer P, Baeuerle PA. Mode of cytotoxic action of T cell-engaging BiTE antibody MT110. Immunobiology 2009; 214:441-53; PMID:19157637; http://dx.doi.org/10.1016/j.imbio.2008.11.014
   PubMed Web of Science ®Google Scholar
• Maloney DG, Grillo-Lopez AJ, Bodkin DJ, White CA, Liles TM, Royston I, Varns C, Rosenberg J, Levy R. IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma. J Clin Oncol 1997; 15:3266-74; PMID:9336364
   PubMed Web of Science ®Google Scholar
• Igawa T, Tsunoda H, Kikuchi Y, Yoshida M, Tanaka M, Koga A, Sekimori Y, Orita T, Aso Y, Hattori K, et al. VH/VL interface engineering to promote selective expression and inhibit conformational isomerization of thrombopoietin receptor agonist single-chain diabody. Protein Eng Des Sel 2010; 23:667-77; PMID:20576629; http://dx.doi.org/10.1093/protein/gzq034
   PubMed Web of Science ®Google Scholar
• Tan PH, Sandmaier BM, Stayton PS. Contributions of a highly conserved VH/VL hydrogen bonding interaction to scFv folding stability and refolding efficiency. Biophys J 1998; 75:1473-82; PMID:9726949; http://dx.doi.org/10.1016/S0006-3495(98)74066-4
   PubMed Web of Science ®Google Scholar
• Kipriyanov SM, Moldenhauer G, Schuhmacher J, Cochlovius B, Von der Lieth CW, Matys ER, Little M. Bispecific tandem diabody for tumor therapy with improved antigen binding and pharmacokinetics. J Mol Biol 1999; 293:41-56; PMID:10512714; http://dx.doi.org/10.1006/jmbi.1999.3156
   PubMed Web of Science ®Google Scholar
• Arndt MA, Krauss J, Kipriyanov SM, Pfreundschuh M, Little M. A bispecific diabody that mediates natural killer cell cytotoxicity against xenotransplantated human Hodgkin's tumors. Blood 1999; 94:2562-8; PMID:10515858
   PubMed Web of Science ®Google Scholar
• Moore PA, Zhang W, Rainey GJ, Burke S, Li H, Huang L, Gorlatov S, Veri MC, Aggarwal S, Yang Y, et al. Application of dual affinity retargeting molecules to achieve optimal redirected T-cell killing of B-cell lymphoma. Blood 2011; 117:4542-51; PMID:21300981; http://dx.doi.org/10.1182/blood-2010-09-306449
   PubMed Web of Science ®Google Scholar
• May C, Sapra P, Gerber HP. Advances in bispecific biotherapeutics for the treatment of cancer. Biochem Pharmacol 2012; 84:1105-12; PMID:22858161; http://dx.doi.org/10.1016/j.bcp.2012.07.011
   PubMed Web of Science ®Google Scholar
• Chichili GR, Huang L, Li H, Burke S, He L, Tang Q, Jin L, Gorlatov S, Ciccarone V, Chen F, et al. A CD3xCD123 bispecific DART for redirecting host T cells to myelogenous leukemia: preclinical activity and safety in nonhuman primates. Sci Transl Med 2015; 7:289ra82; PMID:26019218; http://dx.doi.org/10.1126/scitranslmed.aaa5693
   PubMed Web of Science ®Google Scholar
• Chen S, Huang Q, Liu J, Xing J, Zhang N, Liu Y, Wang Z, Li Q. A targeted IL-15 fusion protein with potent anti-tumor activity. Cancer Biol Ther 2015; 16:1415-21; PMID:26176990; http://dx.doi.org/10.1080/15384047.2015.1071739
   PubMed Web of Science ®Google Scholar
• Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 2007; 7:715-25; PMID:17703228; http://dx.doi.org/10.1038/nri2155
   PubMed Web of Science ®Google Scholar
• Gold DV, Goldenberg DM, Karacay H, Rossi EA, Chang CH, Cardillo TM, McBride WJ, Sharkey RM. A novel bispecific, trivalent antibody construct for targeting pancreatic carcinoma. Cancer Res 2008; 68:4819-26; PMID:18559529; http://dx.doi.org/10.1158/0008-5472.CAN-08-0232
   PubMed Web of Science ®Google Scholar
• Liddy N, Bossi G, Adams KJ, Lissina A, Mahon TM, Hassan NJ, Gavarret J, Bianchi FC, Pumphrey NJ, Ladell K, et al. Monoclonal TCR-redirected tumor cell killing. Nat Med 2012; 18:980-7; PMID:22561687; http://dx.doi.org/10.1038/nm.2764
   PubMed Web of Science ®Google Scholar
• Dahan R, Reiter Y. T-cell-receptor-like antibodies - generation, function and applications. Expert Rev Mol Med 2012; 14:e6; PMID:22361332
   PubMed Web of Science ®Google Scholar
• Reusch U, Burkhardt C, Fucek I, Le Gall F, Le Gall M, Hoffmann K, Knackmuss SH, Kiprijanov S, Little M, Zhukovsky EA. A novel tetravalent bispecific TandAb (CD30/CD16A) efficiently recruits NK cells for the lysis of CD30+ tumor cells. MAbs 2014; 6:728-39; PMID:24670809
   PubMed Web of Science ®Google Scholar
• Schmohl JU, Gleason MK, Dougherty PR, Miller JS, Vallera DA. Heterodimeric Bispecific Single Chain Variable Fragments (scFv) Killer Engagers (BiKEs) Enhance NK-cell Activity Against CD133+ Colorectal Cancer Cells. Target Oncol 2015; 1-9; PMID:24590691
   PubMed Web of Science ®Google Scholar
• Gleason MK, Ross JA, Warlick ED, Lund TC, Verneris MR, Wiernik A, Spellman S, Haagenson MD, Lenvik AJ, Litzow MR. CD16xCD33 bispecific killer cell engager (BiKE) activates NK cells against primary MDS and MDSC CD33+ targets. Blood 2014; 123:3016-26; PMID:24652987; http://dx.doi.org/10.1182/blood-2013-10-533398
   PubMed Web of Science ®Google Scholar
• Vallera DA, Felices M, McElmurry RT, McCullar V, Zhou X, Schmohl J, Zhang B, Lenvik A, Panoskaltsis-Mortari A, Verneris MR. IL-15 trispecific killer engagers (TriKEs) make natural killer cells specific to CD33+ targets while also inducing in vivo expansion, and enhanced function. Clin Cancer Res 2016; clincanres. 2710.015; PMID:26847056
   PubMed Web of Science ®Google Scholar
• Dong B, Zhou C, He P, Li J, Chen S, Miao J, Li Q, Wang Z. A novel bispecific antibody, BiSS, with potent anti-cancer activities. Cancer Biol Ther 2016; 17:364-70; PMID:26828900
   PubMed Web of Science ®Google Scholar
• Davies J, Riechmann L. Antibody VH domains as small recognition units. Biotechnology (N Y) 1995; 13:475-9; PMID:9634788
   PubMedGoogle Scholar
• van den Beucken T, van Neer N, Sablon E, Desmet J, Celis L, Hoogenboom HR, Hufton SE. Building novel binding ligands to B7.1 and B7.2 based on human antibody single variable light chain domains. J Mol Biol 2001; 310:591-601; PMID:11439026; http://dx.doi.org/10.1006/jmbi.2001.4703
   PubMed Web of Science ®Google Scholar
• Ward ES, Gussow D, Griffiths AD, Jones PT, Winter G. Binding activities of a repertoire of single immunoglobulin variable domains secreted from Escherichia coli. Nature 1989; 341:544-6; PMID:2677748; http://dx.doi.org/10.1038/341544a0
   PubMed Web of Science ®Google Scholar
• Pain C, Dumont J, Dumoulin M. Camelid single-domain antibody fragments: Uses and prospects to investigate protein misfolding and aggregation, and to treat diseases associated with these phenomena. Biochimie 2015; 111:82-106; PMID:25656912; http://dx.doi.org/10.1016/j.biochi.2015.01.012
   PubMed Web of Science ®Google Scholar
• Serge M, Padlan EA. Nanobodies: Natural Single-Domain Antibodies. Annu Rev Biochem 2013; 82:775-97; PMID:23495938; http://dx.doi.org/10.1146/annurev-biochem-063011-092449
   PubMed Web of Science ®Google Scholar
• van der Linden RHJ, Frenken LGJ, de Geus B, Harmsen MM, Ruuls RC, Stok W, de Ron L, Wilson S, Davis P, Verrips CT. Comparison of physical chemical properties of llama VHH antibody fragments and mouse monoclonal antibodies. Biochim Biophys Acta 1999; 1431:37-46
   PubMed Web of Science ®Google Scholar
• Dumoulin M, Conrath K, Van Meirhaeghe A, Meersman F, Heremans K, Frenken LGJ, Muyldermans S, Wyns L, Matagne A. Single-domain antibody fragments with high conformational stability. Protein Sci 2002; 11:500-15; PMID:11847273; http://dx.doi.org/10.1110/ps.34602
   PubMed Web of Science ®Google Scholar
• Dolk E, van der Vaart M, Lutje Hulsik D, Vriend G, de Haard H, Spinelli S, Cambillau C, Frenken L, Verrips T. Isolation of llama antibody fragments for prevention of dandruff by phage display in shampoo. Appl Environ Microbiol 2005; 71:442-50; PMID:15640220; http://dx.doi.org/10.1128/AEM.71.1.442-450.2005
   PubMed Web of Science ®Google Scholar
• Stanfield RL, Dooley H, Flajnik MF, Wilson IA. Crystal structure of a shark single-domain antibody V region in complex with lysozyme. Science 2004; 305:1770-3; PMID:15319492; http://dx.doi.org/10.1126/science.1101148
   PubMed Web of Science ®Google Scholar
• Ghannam A, Kumari S, Muyldermans S, Abbady AQ. Camelid nanobodies with high affinity for broad bean mottle virus: a possible promising tool to immunomodulate plant resistance against viruses. Plant Mol Biol 2015; 87:355-69; PMID:25648551; http://dx.doi.org/10.1007/s11103-015-0282-5
   PubMed Web of Science ®Google Scholar
• Cortez-Retamozo V, Backmann N, Senter PD, Wernery U, De Baetselier P. Efficient cancer therapy with a nanobody-based conjugate. Cancer Res 2004; 64:2853; PMID:15087403; http://dx.doi.org/10.1158/0008-5472.CAN-03-3935
   PubMed Web of Science ®Google Scholar
• Baral TN, Magez S, Stijlemans B, Conrath K, Vanhollebeke B. Experimental therapy of African trypanosomiasis with a nanobody-conjugated human trypanolytic factor. Nat Med 2006; 12:580; PMID:16604085; http://dx.doi.org/10.1038/nm1395
   PubMed Web of Science ®Google Scholar
• Kijanka M, Warnders FJ, El Khattabi M, Lub-de Hooge M, van Dam GM, Ntziachristos V, de Vries L, Oliveira S, van Bergen En Henegouwen PM. Rapid optical imaging of human breast tumour xenografts using anti-HER2 VHHs site-directly conjugated to IRDye 800CW for image-guided surgery. Eur J Nucl Med Mol Imaging 2013; 40:1718-29; PMID:23778558; http://dx.doi.org/10.1007/s00259-013-2471-2
   PubMed Web of Science ®Google Scholar
• Vincke C, Loris R, Saerens D, Martinez-Rodriguez S, Muyldermans S, Conrath K. General strategy to humanize a camelid single-domain antibody and identification of a universal humanized nanobody scaffold. J Biol Chem 2009; 284:3273; PMID:19010777; http://dx.doi.org/10.1074/jbc.M806889200
   PubMed Web of Science ®Google Scholar
• Desmyter A, Transue TR, Ghahroudi MA, Thi MH, Poortmans F, Hamers R, Muyldermans S, Wyns L. Crystal structure of a camel single-domain VH antibody fragment in complex with lysozyme. Nat Struct Biol 1996; 3:803-11; PMID:8784355; http://dx.doi.org/10.1038/nsb0996-803
   PubMedGoogle Scholar
• Conrath KE, Lauwereys M, Wyns L, Muyldermans S. Camel single-domain antibodies as modular building units in bispecific and bivalent antibody constructs. J Biol Chem 2001; 276:7346; PMID:11053416; http://dx.doi.org/10.1074/jbc.M007734200
   PubMed Web of Science ®Google Scholar
• Rozan C, Cornillon A, Petiard C, Chartier M, Behar G, Boix C, Kerfelec B, Robert B, Pelegrin A, Chames P, et al. Single-domain antibody-based and linker-free bispecific antibodies targeting FcgammaRIII induce potent antitumor activity without recruiting regulatory T cells. Mol Cancer Ther 2013; 12:1481-91; PMID:23757164; http://dx.doi.org/10.1158/1535-7163.MCT-12-1012
   PubMed Web of Science ®Google Scholar
• Turini M, Chames P, Bruhns P, Baty D, Kerfelec B. A FcgammaRIII-engaging bispecific antibody expands the range of HER2-expressing breast tumors eligible to antibody therapy. Oncotarget 2014; 5:5304-19; PMID:24979648; http://dx.doi.org/10.18632/oncotarget.2093
   PubMed Web of Science ®Google Scholar
• Li L, He P, Zhou C, Jing L, Dong B, Chen S, Zhang N, Liu Y, Miao J, Wang Z, et al. A novel bispecific antibody, S-Fab, induces potent cancer cell killing. J Immunother 2015; 38:350-6; PMID:26448579; http://dx.doi.org/10.1097/CJI.0000000000000099
   PubMed Web of Science ®Google Scholar
• Watson IR, Takahashi K, Futreal PA, Chin L. Emerging patterns of somatic mutations in cancer. Nat Rev Genet 2013; 14:703-18; PMID:24022702; http://dx.doi.org/10.1038/nrg3539
   PubMed Web of Science ®Google Scholar