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双特异性抗体研发进展

来源：药物分析杂志 2019, Vol. 39 Issue (1): 78-85. DOI: 10.16155/j.0254-1793.2019.01.10

张峰 , 王开芹 , 王兰     

摘要：双特异性抗体（bsAb）因可同时特异性结合2个不同抗原表位，拓展了治疗性单克隆抗体的临床应用范围。制备bsAb需要对传统的抗体结构进行改造，在此过程中衍生出了数十种结构，不同的结构具有不同的作用特点。本综述就当前典型的bsAb结构及其原理进行介绍，对bsAb的作用原理进行分析，并对当前代表性的bsAb的研发阶段进行了简单总结。
关键词：双特异性抗体（bsAb）    单克隆抗体    抗体结构    研发    进展    
Development in bispecific antibody
ZHANG Feng, WANG Kai-qin, WANG Lan    
Abstract: The clinical application of therapeutic monoclonal antibody has been extended by bispesific antibody (bsAb)due to their capacity of binding two different antigenic epitopes.Structure changing would be needed for the construction of bsAb.There are several tens of bsAb structures developed, the specific action characteristics of which are related with their unique bsAb structure.In this review, typical structures and acting principles of bsAb were introduced, the action principle of bsAb was analyzed, and the development stages of representative bsAb were briefly summarized.
Key words: bispecific antibody(bsAb)    monoclonal antibody    antibody structure    research    development    

双特异性抗体研发进展

药物分析杂志 2019, Vol. 39 Issue (1): 78-85. DOI: 10.16155/j.0254-1793.2019.01.10



参考文献

[1]
COLOMA MJ, MORRISON SL. Design and production of novel tetravalent bispecific antibodies[J]. Nat Biotechnol, 1997, 15(2): 159. DOI:10.1038/nbt0297-159
[2]
CHAN AC, CARTER PJ. Therapeutic antibodies for autoimmunity and inflammation[J]. Nat Rev Immunol, 2010, 10(5): 301. DOI:10.1038/nri2761
[3]
KONTERMANN RE. Dual targeting strategies with bispecific antibodies[J]. MAbs, 2012, 4(2): 182. DOI:10.4161/mabs.4.2.19000
[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. DOI:10.1016/j.tibtech.2013.08.007
[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. DOI:10.1093/protein/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. DOI:10.1074/jbc.M110.117382
[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. DOI:10.4161/mabs.3.6.18123
[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. DOI:10.1093/protein/gzp094
[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. DOI:10.1093/protein/gzq034
[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. DOI:10.1073/pnas.1019002108
[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. DOI:10.1073/pnas.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. DOI:10.1016/S0022-1759(00)00339-2
[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. DOI:10.1093/protein/gzq123
[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. DOI:10.1074/jbc.M112.397869
[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. DOI:10.1074/jbc.M110.113910
[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. DOI:10.4161/mabs.23043
[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. DOI:10.4161/mabs.23977
[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. DOI:10.1038/nbt1345
[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. DOI:10.1093/protein/gzm061
[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. DOI:10.1016/S0006-3495(98)74066-4
[26]
PERCHIACCA JM, TESSIER PM. Engineering aggregation-resistant antibodies[J]. Annu Rev Chem Biomol Eng, 2012, 3: 263. DOI:10.1146/annurev-chembioeng-062011-081052
[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. DOI:10.1016/S1359-6446(05)03554-3
[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. DOI:10.1074/jbc.M700820200
[29]
OATES J, JAKOBSEN BK. ImmTACs:novel bi-specific agents for targeted cancer therapy[J]. Oncoimmunology, 2013, 2(2): e22891. DOI:10.4161/onci.22891
[30]
DOPPALAPUDI VR, HUANG J, LIU D, et al. Chemical generation of bispecific antibodies[J]. Proc Natl Acad Sci USA, 2010, 107(52): 22611. DOI:10.1073/pnas.1016478108
[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. DOI:10.1186/s13045-015-0109-5
[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. DOI:10.1016/j.drudis.2015.02.008
[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. DOI:10.1158/1535-7163.MCT-11-0820
[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. DOI:10.1158/1535-7163.MCT-13-0255
[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. DOI:10.1158/1078-0432.CCR-17-0646
[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. DOI:10.1158/1078-0432.CCR-13-0081
[39]
WILLIAMS SC. Small nanobody drugs win big backing from pharma[J]. Nat Med, 2013, 19(11): 1355. DOI:10.1038/nm1113-1355
[40]

KINGWELL K. InterMune and Boehringer blaze trails for idiopathic pulmonary fibrosis drugs[J]. Nat Rev Drug Discov, 2014, 13(7): 483. DOI:10.1038/nrd4382

双特异性抗体研发进展

药物分析杂志 2019, Vol. 39 Issue (1): 78-85. DOI: 10.16155/j.0254-1793.2019.01.10

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