[1] COLOMA MJ,MORRISON SL.Design and production of novel tetravalent bispecific antibodies[J].Nat Biotechnol,1997,15(2):159
[2] CHAN AC,CARTER PJ.Therapeutic antibodies for autoimmunity and inflammation[J].Nat Rev Immunol,2010,10(5):301
[3] KONTERMANN RE.Dual targeting strategies with bispecific antibodies[J].MAbs,2012,4(2):182
[4] BYRNE H,CONROY PJ,WHISSTOCK JC,et al.A tale of two specificities:bispecific antibodies for therapeutic and diagnostic applications[J].Trends Biotechnol,2013,31(11):621
[5] JOST C,PLUCKTHUN A.Engineered proteins with desired specificity:DARPins,other alternative scaffolds and bispecific IgGs[J].Curr Opin Struct Biol,2014,27:102
[6] RIDGWAY JB,PRESTA LG,CARTER P.'Knobs-into-holes' engineering of antibody CH3 domains for heavy chain heterodimerization[J].Protein Eng,1996,9(7):617
[7] YAN L,BECKMAN R.Pharmacogenetics and pharmacogenomics in oncology therapeutic antibody development[J].Biotechniques,2005,39(10 Suppl):S565
[8] GUNASEKARAN K,PENTONY M,SHEN M,et al.Enhancing antibody Fc heterodimer formation through electrostatic steering effects:applications to bispecific molecules and monovalent IgG[J].J Biol Chem,2010,285(25):19637
[9] MOORE GL,BAUTISTA C,PONG E,et al.A novel bispecific antibody format enables simultaneous bivalent and monovalent co-engagement of distinct target antigens[J].mAbs,2011,3(6):546
[10] DAVIS JH,APERLO C,LI Y,et al.SEED bodies:fusion proteins based on strand-exchange engineered domain (SEED)CH3 heterodimers in an Fc analogue platform for asymmetric binders or immunofusions and bispecific antibodies[J].Protein Eng Des Sel,2010,23(4):195
[11] ZHU Z,PRESTA LG,ZAPATA G,et al.Remodeling domain interfaces to enhance heterodimer formation[J].Protein Sci,1997,6(4):781
[12] IGAWA T,TSUNODA H,KIKUCHI Y,et al.VH/VL interface engineering to promote selective expression and inhibit conformational isomerization of thrombopoietin receptor agonist single-chain diabody[J].Protein Eng Des Sel,2010,23(8):667
[13] SCHAEFER W,REGULA JT,BAHNER M,et al.Immunoglobulin domain crossover as a generic approach for the production of bispecific IgG antibodies[J].Proc Natl Acad Sci USA,2011,108(27):11187
[14] YAN L,BECKMAN RA.Pharmacogenetics and pharmacogenomics in oncology therapeutic antibody development[J].Biotechniques,2005,39(4):565
[15] STAERZ UD,BEVAN MJ.Hybrid hybridoma producing a bispecific monoclonal antibody that can focus effector T-cell activity[J].Proc Natl Acad Sci USA,1986,83(5):1453
[16] ZEIDLER R,REISBACH G,WOLLENBERG B,et al.Simultaneous activation of T cells and accessory cells by a new class of intact bispecific antibody results in efficient tumor cell killing[J].J Immunol,1999,163(3):1246
[17] CARTER P.Bispecific human IgG by design[J].J Immunol Methods,2001,248(1-2):7
[18] MUDA M,GROSS AW,DAWSON JP,et al.Therapeutic assessment of SEED:a new engineered antibody platform designed to generate mono-and bispecific antibodies[J].Protein Eng Des Sel,2011,24(5):447
[19] WRANIK BJ,CHRISTENSEN EL,SCHAEFER G,et al.LUZ-Y,a novel platform for the mammalian cell production of full-length IgG-bispecific antibodies[J].J Biol Chem,2012,287(52):43331
[20] JACKMAN J,CHEN Y,HUANG A,et al.Development of a two-part strategy to identify a therapeutic human bispecific antibody that inhibits IgE receptor signaling[J].J Biol Chem,2010,285(27):20850
[21] LAFLEUR DW,ABRAMYAN D,KANAKARAJ P,et al.Monoclonal antibody therapeutics with up to five specificities:functional enhancement through fusion of target-specific peptides[J].MAbs,2013,5(2):208
[22] JAKOB CG,EDALJI R,JUDGE RA,et al.Structure reveals function of the dual variable domain immunoglobulin (DVD-Ig)molecule[J].MAbs,2013,5(3):358
[23] WU C,YING H,GRINNELL C,et al.Simultaneous targeting of multiple disease mediators by a dual-variable-domain immunoglobulin[J].Nat Biotechnol,2007,25(11):1290
[24] STORK R,MULLER D,KONTERMANN RE.A novel tri-functional antibody fusion protein with improved pharmacokinetic properties generated by fusing a bispecificsingle-chain diabody with an albumin-binding domain from streptococcal protein G[J].Protein Eng Des Sel,2007,20(11):569
[25] TAN PH,SANDMAIER BM,STAYTON PS.Contributions of a highly conserved VH/VL hydrogen bonding interaction to scFv folding stability and refolding efficiency[J].Biophys J,1998,75(3):1473
[26] PERCHIACCA JM,TESSIER PM.Engineering aggregation-resistant antibodies[J].Annu Rev Chem Biomol Eng,2012,3:263
[27] WOLF E,HOFMEISTER R,KUFER P,et al.BiTEs:bispecific antibody constructs with unique anti-tumor activity[J].Drug Discov Today,2005,10(18):1237
[28] MULLER D,KARLE A,MEISSBURGER B,et al.Improved pharmacokinetics of recombinant bispecific antibody molecules by fusion to human serum albumin[J].J Biol Chem,2007,282(17):12650
[29] OATES J,JAKOBSEN BK.ImmTACs:novel bi-specific agents for targeted cancer therapy[J].Oncoimmunology,2013,2(2):e22891
[30] DOPPALAPUDI VR,HUANG J,LIU D,et al.Chemical generation of bispecific antibodies[J].Proc Natl Acad Sci USA,2010,107(52):22611
[31] SPIESS C,ZHAI Q,CARTER PJ.Alternative molecular formats and therapeutic applications for bispecific antibodies[J].Mol Immunol,2015,67(2 PtA):95
[32] FAN D,LI Z,ZHANG X,et al.AntiCD3Fv fused to human interleukin-3 deletion variant redirected T cells against human acute myeloid leukemic stem cells[J].J Hematol Oncol,2015, 8:18
[33] ZUGMAIER G,KLINGER M,SCHMIDT M,et al.Clinical overview of anti-CD19 BiTE((R))and ex vivo data from anti-CD33 BiTE((R))as examples for retargeting T cells in hematologic malignancies[J].Mol Immunol,2015,67(2 PtA):58
[34] KONTERMANN RE,BRINKMANN U.Bispecific antibodies[J].Drug Discov Today,2015,20(7):838
[35] MCDONAGH CF,HUHALOV A,HARMS BD,et al.Antitumor activity of a novel bispecific antibody that targets the ErbB2/ErbB3 oncogenic unit and inhibits heregulin-induced activation of ErbB3[J].Mol Cancer Ther,2012,11(3):582
[36] FITZGERALD JB,JOHNSON BW,BAUM J,et al.MM-141,an IGF-IR-and ErbB3-directed bispecific antibody,overcomes network adaptations that limit activity of IGF-IR inhibitors[J]. Mol Cancer Ther,2014,13(2):410
[37] HILL AG,FINDLAY MP,BURGE ME,et al.Phase Ⅱ study of the dual EGFR/HER3 inhibitor duligotuzumab (MEHD7945A)versus cetuximab in combination with FOLFIRI in second-line RAS wild-type metastatic colorectal cancer[J].Clin Cancer Res,2018,24(10):2276
[38] KIENAST Y,KLEIN C,SCHEUER W,et al.Ang-2-VEGF-A Cross Mab,a novel bispecific human IgG1 antibody blocking VEGF-A and Ang-2 functions simultaneously,mediates potent antitumor,antiangiogenic,and antimetastatic efficacy[J].Clin Cancer Res,2013,19(24):6730
[39] WILLIAMS SC.Small nanobody drugs win big backing from pharma[J].Nat Med,2013,19(11):1355
[40] KINGWELL K.InterMune and Boehringer blaze trails for idiopathic pulmonary fibrosis drugs[J].Nat Rev Drug Discov,2014,13(7):483