Skip to main content
SpringerLink
Log in

Diabodies, Single-Chain Diabodies, and Their Derivatives

  • Chapter
  • First Online:
Bispecific Antibodies

Abstract

The fragment variable (Fv) represents the smallest part of an antibody containing the entire antigen binding site formed by the variable heavy and light chain domains (VH and VL) (Filpula and McGuire 1999; Chames et al. 2009; Kontermann 2010). Because of the noncovalent interaction between the VH and VL domain, Fv molecules suffer from instability, which can be improved by connecting the two domains with a flexible peptide linker. These single-chain Fv (scFv) fragments can be easily produced in prokaryotic and eukaryotic systems and represent the prototype recombinant antibody format.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alfthan K, Takkinen K, Sizmann D, Söderlund H, Teeri TT (1995) Properties of a single-chain antibody containing different linker peptides. Protein Eng 8:725–731

    Article  CAS  PubMed  Google Scholar 

  • Alt M, Müller R, Kontermann RE (1999) Novel tetravalent and bispecific IgG-like antibody molecules combining single-chain diabodies with the immunoglobulin g1 Fc or CH3 region. FEBS Lett 454:90–94

    Article  CAS  PubMed  Google Scholar 

  • Arndt KM, Müller KM, Plückthun A (1998) Factors influencing the dimer to monomer transition of an antibody single-chain Fv fragment. Biochemistry 37:12918–12926

    Article  CAS  PubMed  Google Scholar 

  • Arndt MA, Krauss J, Kipriyanov SM, Pfreundschuh M, Little M (1999) A bispecific diabody that mediates natural killer cell cytotoxicity against xenotransplantated human Hodgkin’s tumors. Blood 94(8):2562–2568

    CAS  PubMed  Google Scholar 

  • Asano R, Kudo T, Nishimura Y, Makabe K, Hayashi H, Suzuki M, Tsumoto K, Kumagai I (2002) Efficient construction of a diabody using a refolding system: anti-carcinoembryonic antigen recombinant antibody fragment. J Biochem 132(6):903–909

    Article  CAS  PubMed  Google Scholar 

  • Asano R, Kawaguchi H, Watanabe Y, Nakanishi T, Umetsu M, Hayashi H, Katayose Y, Unno M, Kudo T, Kumagai I (2008) Diabody-based recombinant formats of humanized IgG-like bispecific antibody with effective retargeting of lymphocytes to tumor cells. J Immunother 31(8):752–761

    Article  CAS  PubMed  Google Scholar 

  • Blanco B, Holliger P, Vile RG, Alvarez-Vallina L (2003) Induction of human T lymphocyte cytotoxicity and inhibition of tumor growth by tumor-specific diabody-based molecules secreted from gene-modified bystander cells. J Immunol 171(2):1070–1077

    CAS  PubMed  Google Scholar 

  • Brüsselbach S, Korn T, Völkel T, Müller R, Kontermann RE (1999) Enzyme recruitment and tumor cell killing in vitro by a secreted bispecific single-chain diabody. Tumor Target 4:115–123

    Google Scholar 

  • Bühler P, Wolf P, Gierschner D, Schaber I, Katzenwadel A, Schultze-Seemann W, Wetterauer U, Tacke M, Swamy M, Schamel WW, Elsässer-Beile U (2008) A bispecific diabody directed against prostate-specific membrane antigen and CD3 induces T-cell mediated lysis of prostate cancer cells. Cancer Immunol Immunother 57(1):43–52

    Article  PubMed  Google Scholar 

  • Bühler P, Molnar E, Dopfer EP, Wolf P, Gierschner D, Wetterauer U, Schamel WW, Elsässer-Beile U (2009) Target-dependent T-cell activation by coligation with a PSMA x CD3 diabody induces lysis of prostate cancer cells. J Immunother 32(6):565–573

    Article  PubMed  Google Scholar 

  • Carmichael JA, Power BE, Garrett TPJ, Yazaki PJ, Shively JE, Raubischek AA, Wu AM, Hudson PJ (2003) The crystal structure of an anti-CEA diabody assembled from T84.66 scFvs in VL-to-VH orientation: implications for diabody flexibility. J Mol Biol 326:341–361

    Article  CAS  PubMed  Google Scholar 

  • Chames P, Van Regenmortel M, Weiss E, Baty D (2009) Therapeutic antibodies: successes, limitations and hopes for the future. Br J Pharmacol 157:220–233

    Article  CAS  PubMed  Google Scholar 

  • Cochlovius B, Kipriyanov SM, Stassar MJ, Schuhmacher J, Benner A, Moldenhauer G, Little M (2000a) Cure of Burkitt’s lymphoma in severe combined immunodeficiency mice by T cells, tetravalent CD3 x CD19 tandem diabody, and CD28 costimulation. Cancer Res 60(16):4336–4341

    CAS  PubMed  Google Scholar 

  • Cochlovius B, Kipriyanov SM, Stassar MJ, Christ O, Schuhmacher J, Strauss G, Moldenhauer G, Little M (2000b) Treatment of human B cell lymphoma xenografts with a CD3 x CD19 diabody and T cells. J Immunol 165(2):888–895

    CAS  PubMed  Google Scholar 

  • Compte M, Blanco B, Serrano F, Cuesta AM, Sanz L, Bernad A, Holliger P, Alvarez-Vallina L (2007) Inhibition of tumor growth in vivo by in situ secretion of bispecific anti-CEA x anti-CD3 diabodies from lentivirally transduced human lymphocytes. Cancer Gene Ther 14(4):380–388

    Article  CAS  PubMed  Google Scholar 

  • Compte M, Cuesta AM, Sánchez-Martín D, Alonso-Camino V, Vicario JL, Sanz L, Alvarez-Vallina L (2009) Tumor immunotherapy using gene-modified human mesenchymal stem cells loaded into synthetic extracellular matrix scaffolds. Stem Cells 27(3):753–760

    Article  CAS  PubMed  Google Scholar 

  • Compte M, Alonso-Camino V, Santos-Valle P, Cuesta AM, Sánchez-Martín D, López MR, Vicario JL, Salas C, Sanz L, Alvarez-Vallina L (2010) Factory neovessels: engineered human blood vessels secreting therapeutic proteins as a new drug delivery system. Gene Ther 17(6):745–751

    Article  CAS  PubMed  Google Scholar 

  • DeNardo DG, Xiong CY, Shi XB, DeNardo GL, DeNardo SJ (2001) Anti-HLA-DR/anti-DOTA diabody construction in a modular gene design platform: bispecific antibodies for pretargeted radioimmunotherapy. Cancer Biother Radiopharm 16(6):525–535

    Article  CAS  PubMed  Google Scholar 

  • Develter J, Booth NA, Declerck PJ, Gils A (2008) Bispecific targeting of thrombin activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 by a heterodimer diabody. J Thromb Haemost 6(11):1884–1891

    Article  CAS  PubMed  Google Scholar 

  • Essig NZ, Wood JF, Howard AJ, Raag R, Whitlow M (1993) Crystallization of single-chain Fv proteins. J Mol Biol 234:897–901

    Article  CAS  PubMed  Google Scholar 

  • Filpula D, McGuire J (1999) Single-chain Fv designs for protein, cell and gene therapeutics. Exp Opin Ther Patents 9:231–245

    Article  CAS  Google Scholar 

  • Fitzgerald K, Holliger P, Winter G (1997) Improved tumour targeting by disulphide stabilized diabodies expressed in Pichia pastoris. Protein Eng 10:1221–1225

    Article  CAS  PubMed  Google Scholar 

  • Gao Y, Xiong D, Yang M, Liu H, Peng H, Shao X, Xu Y, Xu C, Fan D, Qin L, Yang C, Zhu Z (2004) Efficient inhibition of multidrug-resistant human tumors with a recombinant bispecific anti-P-glycoprotein x anti-CD3 diabody. Leukemia 18(3):513–520

    Article  CAS  PubMed  Google Scholar 

  • Griffiths GL, Chang CH, McBride WJ, Rossi EA, Sheerin A, Tejada GR, Karacay H, Sharkey RM, Horak ID, Hansen HJ, Goldenberg DM (2004) Reagents and methods for PET using bispecific antibody pretargeting and 68Ga-radiolabeled bivalent hapten-peptide-chelate conjugates. J Nucl Med 45(1):30–39

    CAS  PubMed  Google Scholar 

  • Guo H, Jiang W, Liu W, Gao Y, Yang M, Zhou Y, Wang J, Qi J, Cheng X, Zhu Z, Yang C, Xiong D (2008) Extracellular domain of 4-1BBL enhanced the antitumoral efficacy of peripheral blood lymphocytes mediated by anti-CD3 x anti-Pgp bispecific diabody against human multidrug-resistant leukemia. Cell Immunol 251(2):102–108

    Article  CAS  PubMed  Google Scholar 

  • Hayashi H, Asano R, Tsumoto K, Katayose Y, Suzuki M, Unno M, Kodama H, Takemura S, Yoshida H, Makabe K, Imai K, Matsuno S, Kumagai I, Kudo T (2004) A highly effective and stable bispecific diabody for cancer immunotherapy: cure of xenografted tumors by bispecific diabody and T-LAK cells. Cancer Immunol Immunother 53(6):497–509

    Article  CAS  PubMed  Google Scholar 

  • Helfrich W, Kroesen BJ, Roovers RC, Westers L, Molema G, Hoogenboom HR, de Leij L (1998) Construction and characterization of a bispecific diabody for retargeting T cells to human carcinomas. Int J Cancer 76(2):232–239

    Article  CAS  PubMed  Google Scholar 

  • Holliger P, Prospero T, Winter G (1993) “Diabodies”: small bivalent and bispecific antibody fragments. Proc Natl Acad Sci USA 90:6444–6448

    Article  CAS  PubMed  Google Scholar 

  • Holliger P, Brissinck J, Williams RL, Thielemans K, Winter G (1996) Specific killing of lymphoma cells by cytotoxic T-cells mediated by a bispecific diabody. Protein Eng 9(3):299–305

    Article  CAS  PubMed  Google Scholar 

  • Holliger P, Wing M, Pound JD, Bohlen H, Winter G (1997) Retargeting serum immunoglobulin with bispecific diabodies. Nat Biotechnol 15(7):632–636

    Article  CAS  PubMed  Google Scholar 

  • Holliger P, Manzke O, Span M, Hawkins R, Fleischmann B, Qinghua L, Wolf J, Diehl V, Cochet O, Winter G, Bohlen H (1999) Carcinoembryonic antigen (CEA)-specific T-cell activation in colon carinoma induced by anti-CD3 x anti-CEA bispecific diabodies and B7 x anti-CEA bispecific fusion proteins. Cancer Res 59:2909–2916

    CAS  PubMed  Google Scholar 

  • Hopp J, Hornig N, Zettlitz KA, Schwarz A, Fuß N, Müller D, Kontermann RE (2010) The effects of affinity and valency of an albumin-binding domain (ABD) on the half-life of a single-chain diabody-ABD fusion protein. Protein Eng Des Sel 23:827–834

    Article  CAS  PubMed  Google Scholar 

  • Houtenbos I, Santegoets S, Westers TM, Waisfisz Q, Kipriyanov S, Denkers F, Scheper RJ, de Gruijl TD, Ossenkoppele GJ, van de Loosdrecht AA (2008) The novel bispecific diabody alphaCD40/alphaCD28 strengthens leukaemic dendritic cell-induced T-cell reactivity. Br J Haematol 142(2):273–283

    Article  CAS  PubMed  Google Scholar 

  • Hudson PJ, Kortt AA (1999) High avidity scFv multimers: diabodies and triabodies. J Immunol Meth 231:177–189

    Article  CAS  Google Scholar 

  • Igawa T, Tsunoda H, Kikuchi Y, Yoshida M, Tanaka M, Koga A, Sekimori Y, Orita T, Aso Y, Hattori K, Tsuchiya M (2010) VH/VL interface engineering to promote selective expression and inhibition of conformational isomerization of thrombopoeitin receptor agonist single-chain diabody. Protein Eng Des Sel 23:667–677

    Article  CAS  PubMed  Google Scholar 

  • Iliades P, Kortt AA, Hudson PJ (1997) Triabodies: single chain Fv fragments wihtout a linker form trivalent trimers. FEBS Lett 409:437–441

    Article  CAS  PubMed  Google Scholar 

  • Jimenez X, Lu D, Brennan L, Persaud K, Liu M, Miao H, Witte L, Zhu Z (2005) A recombinant, fully human, bispecific antibody neutralizes the biological activities mediated by both vascular endothelial growth factor receptors 2 and 3. Mol Cancer Ther 4(3):427–434

    CAS  PubMed  Google Scholar 

  • Johnson S, Burke S, Huang L, Gorlatov S, Li H, Wang W, Zhang W, Tuaillon N, Rainey J, Barat B, Yang Y, Jin L, Ciccarone V, Moore PA, Koenig S, Bonvini E (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(3):436–449

    Article  CAS  PubMed  Google Scholar 

  • Kashentseva EA, Douglas JT, Zinn KR, Curiel DT, Dmitriev IP (2009) Targeting of adenovirus serotype 5 pseudotyped with short fiber from serotype 41 to c-erbB2-positive cells using bispecific single-chain diabody. J Mol Biol 388(3):443–461

    Article  CAS  PubMed  Google Scholar 

  • Kipriyanov SM, Moldenhauer G, Strauss G, Little M (1998) Bispecific CD3 x CD19 diabody for T cell-mediated lysis of malignant human B cells. Int J Cancer 77(5):763–772

    Article  CAS  PubMed  Google Scholar 

  • Kipriyanov SM, Moldenhauer G, Schuhmacher J, Cochlovius B, Von der Lieth CW, Matys ER, Little M (1999) Bispecific tandem diabody for tumor therapy with improved antigen binding and pharmacokinetics. J Mol Biol 293(1):41–56

    Article  CAS  PubMed  Google Scholar 

  • Kipriyanov SM, Cochlovius B, Schäfer HJ, Moldenhauer G, Bähre A, Le Gall F, Knackmuss S, Little M (2002) Synergistic antitumor effect of bispecific CD19 x CD3 and CD19 x CD16 diabodies in a preclinical model of non-Hodgkin’s lymphoma. J Immunol 169(1):137–144

    CAS  PubMed  Google Scholar 

  • Kontermann RE (2005) Recombinant bispecific antibodies for cancer therapy. Acta Pharmacol Sin 26(1):1–9

    Article  CAS  PubMed  Google Scholar 

  • Kontermann RE (2009) Strategies to extend plasma half-lives of recombinant antibodies. BioDrugs 23(2):93–109

    Article  CAS  PubMed  Google Scholar 

  • Kontermann RE (2010) Alternative antibody formats. Curr Opin Mol Ther 12(2):176–183

    CAS  PubMed  Google Scholar 

  • Kontermann RE, Wing MG, Winter G (1997) Complement recruitment using bispecific diabodies. Nat Biotechnol 15(7):629–631

    Article  CAS  PubMed  Google Scholar 

  • Korn T, Nettelbeck DM, Völkel T, Müller R, Kontermann RE (2004a) Recombinant bispecific antibodies for the targeting of adenoviruses to CEA-expressing tumour cells: a comparative analysis of bacterially expressed single-chain diabody and tandem scFv. J Gene Med 6(6):642–651

    Article  CAS  PubMed  Google Scholar 

  • Korn T, Müller R, Kontermann RE (2004b) Bispecific single-chain diabody-mediated killing of endoglin-positive endothelial cells by cytotoxic T lymphocytes. J Immunother 27(2):99–106

    Article  CAS  PubMed  Google Scholar 

  • Kortt AA, Dolezal O, Power BE, Hudson PJ (2001) Dimeric and trimeric antibodies: high avidity scFvs for cancer targeting. Biomol Eng 18:95–108

    Article  CAS  PubMed  Google Scholar 

  • Le Gall F, Reusch U, Little M, Kipriyanov SM (2004) Effect of linker sequences between the antibody variable domains on the formation, stability and biological activity of a bispecific tandem diabody. Protein Eng Des Sel 17:357–366

    Article  PubMed  Google Scholar 

  • Liu J, Yang M, Wang J, Xu Y, Wang Y, Shao X, Yang C, Gao Y, Xiong D (2009) Improvement of tumor targeting and antitumor activity by a disulphide bond stabilized diabody expressed in Escherichia coli. Cancer Immunol Immunother 58(11):1761–1769

    Article  CAS  PubMed  Google Scholar 

  • Liu R, Jiang W, Yang M, Guo H, Zhang Y, Wang J, Zhu H, Shi R, Fan D, Yang C, Zhu Z, Xie Y, Xiong D (2010) Efficient inhibition of human B-cell lymphoma in SCID mice by synergistic antitumor effect of human 4-1BB ligand/anti-CD20 fusion proteins and anti-CD3/anti-CD20 diabodies. J Immunother 33(5):500–509

    Article  PubMed  Google Scholar 

  • Lu D, Kotanides H, Jimenez X, Zhou Q, Persaud K, Bohlen P, Witte L, Zhu Z (1999) Acquired antagonistic activity of a bispecific diabody directed against two different epitopes on vascular endothelial growth factor receptor 2. J Immunol Methods 230(1–2):159–171

    Article  CAS  PubMed  Google Scholar 

  • Lu D, Jimenez X, Zhang H, Wu Y, Bohlen P, Witte L, Zhu Z (2001) Complete inhibition of vascular endothelial growth factor (VEGF) activities with a bifunctional diabody directed against both VEGF kinase receptors, fms-like tyrosine kinase receptor and kinase insert domain-containing receptor. Cancer Res 61(19):7002–7008

    CAS  PubMed  Google Scholar 

  • Lu D, Jimenez X, Zhang H, Atkins A, Brennan L, Balderes P, Bohlen P, Witte L, Zhu Z (2003) Di-diabody: a novel tetravalent bispecific antibody molecule by design. J Immunol Methods 279(1–2):219–232

    Article  CAS  PubMed  Google Scholar 

  • Lu D, Jimenez X, Witte L, Zhu Z (2004) The effect of variable domain orientation and arrangement on the antigen-binding activity of a recombinant human bispecific diabody. Biochem Biophys Res Commun 318(2):507–513

    Article  CAS  PubMed  Google Scholar 

  • Lu D, Zhang H, Koo H, Tonra J, Balderes P, Prewett M, Corcoran E, Mangalampalli V, Bassi R, Anselma D, Patel D, Kang X, Ludwig DL, Hicklin DJ, Bohlen P, Witte L, Zhu Z (2005) A fully human recombinant IgG-like bispecific antibody to both the epidermal growth factor receptor and the insulin-like growth factor receptor for enhanced antitumor activity. J Biol Chem 280(20):19665–19672

    Article  CAS  PubMed  Google Scholar 

  • Mølhøj M, Crommer S, Brischwein K, Rau D, Sriskandarajah M, Hoffmann P, Kufer P, Hofmeister R, Baeuerle PA (2007) CD19-/CD3-bispecific antibody of the BiTE class is far superior to tandem diabody with respect to redirected tumor cell lysis. Mol Immunol 44(8):1935–1943

    Article  PubMed  Google Scholar 

  • Müller D, Karle A, Meissburger B, Höfig I, Stork R, Kontermann RE (2007) Improved pharmacokinetics of recombinant bispecific antibody molecules by fusion to human serum albumin. J Biol Chem 282(17):12650–12660

    Article  PubMed  Google Scholar 

  • Müller D, Frey K, Kontermann RE (2008) A novel antibody-4-1BBL fusion protein for targeted costimulation in cancer immunotherapy. J Immunother 31(8):714–722

    Article  PubMed  Google Scholar 

  • Nettelbeck DM, Miller DW, Jérôme V, Zuzarte M, Watkins SJ, Hawkins RE, Müller R, Kontermann RE (2001) Targeting of adenovirus to endothelial cells by a bispecific single-chain diabody directed against the adenovirus fiber knob domain and human endoglin (CD105). Mol Ther 3(6):882–891

    Article  CAS  PubMed  Google Scholar 

  • Nettelbeck DM, Rivera AA, Kupsch J, Dieckmann D, Douglas JT, Kontermann RE, Alemany R, Curiel DT (2004) Retargeting of adenoviral infection to melanoma: combining genetic ablation of native tropism with a recombinant bispecific single-chain diabody (scDb) adapter that binds to fiber knob and HMWMAA. Int J Cancer 108(1):136–145

    Article  CAS  PubMed  Google Scholar 

  • Pei XY, Holliger P, Murzin AG, Williams RL (1997) The 2.0-Å resolution crystal structure of a trimeric antibody fragment with noncognate VH-VL domain paris shows a rearrangement of VH CDR3. Proc Natl Acad Sci USA 94:9637–9642

    Article  CAS  PubMed  Google Scholar 

  • Perisic O, Webb PA, Holliger P, Winter G, Williams RL (1994) Crystal structure of a diabody, a bivalent antibody fragment. Structure 2:1217–1226

    Article  CAS  PubMed  Google Scholar 

  • Reiter Y, Brinkmann U, Lee B, Pastan I (1996) Engineering antibody Fv fragments for cancer detection and therapy: disulfide-stabilized Fv fragments. Nat Biotechnol 14:1239–1245

    Article  CAS  PubMed  Google Scholar 

  • Reusch U, Le Gall F, Hensel M, Moldenhauer G, Ho AD, Little M, Kipriyanov SM (2004) Effect of tetravalent bispecific CD19xCD3 recombinant antibody construct and CD28 costimulation on lysis of malignant B cells from patients with chronic lymphocytic leukemia by autologous T cells. Int J Cancer 112(3):509–518

    Article  CAS  PubMed  Google Scholar 

  • Schlenzka J, Moehler TM, Kipriyanov SM, Kornacker M, Benner A, Bähre A, Stassar MJ, Schäfer HJ, Little M, Goldschmidt H, Cochlovius B (2004) Combined effect of recombinant CD19 x CD16 diabody and thalidomide in a preclinical model of human B cell lymphoma. Anticancer Drugs 15(9):915–919

    Article  CAS  PubMed  Google Scholar 

  • Segal DM, Weiner GJ, Weiner LM (1999) Bispecific antibodies in cancer therapy. Curr Opin Immunol 11:558–562

    Article  CAS  PubMed  Google Scholar 

  • Stork R, Müller D, Kontermann RE (2007) A novel tri-functional antibody fusion protein with improved pharmacokinetic properties generated by fusing a bispecific single-chain diabody with an albumin-binding domain from streptococcal protein G. Protein Eng Des Sel 20(11):569–576

    Article  CAS  PubMed  Google Scholar 

  • Stork R, Zettlitz KA, Müller D, Rether M, Hanisch FG, Kontermann RE (2008) N-glycosylation as novel strategy to improve pharmacokinetic properties of bispecific single-chain diabodies. J Biol Chem 283(12):7804–7812

    Article  CAS  PubMed  Google Scholar 

  • Stork R, Campigna E, Robert B, Müller D, Kontermann RE (2009) Biodistribution of a bispecific single-chain diabody and its half-life extended derivatives. J Biol Chem 284(38):25612–25619

    Article  CAS  PubMed  Google Scholar 

  • Takemura S, Asano R, Tsumoto K, Ebara S, Sakurai N, Katayose Y, Kodama H, Yoshida H, Suzuki M, Imai K, Matsuno S, Kudo T, Kumagai I (2000) Construction of a diabody (small recombinant bispecific antibody) using a refolding system. Protein Eng 13(8):583–588

    Article  CAS  PubMed  Google Scholar 

  • Takemura S, Kudo T, Asano R, Suzuki M, Tsumoto K, Sakurai N, Katayose Y, Kodama H, Yoshida H, Ebara S, Saeki H, Imai K, Matsuno S, Kumagai I (2002) A mutated superantigen SEA D227A fusion diabody specific to MUC1 and CD3 in targeted cancer immunotherapy for bile duct carcinoma. Cancer Immunol Immunother 51(1):33–44

    Article  CAS  PubMed  Google Scholar 

  • Todorovska A, Roovers RC, Dolezal O, Kortt AA, Hoogenboom HR, Hudson RJ (2001) Design and application of diabodies, triabodies and tetrabodies for cancer targeting. J Immunol Meth 248:47–66

    Article  CAS  Google Scholar 

  • Veri MC, Burke S, Huang L, Li H, Gorlatov S, Tuaillon N, Rainey GJ, Ciccarone V, Zhang T, Shah K, Jin L, Ning L, Minor T, Moore PA, Koenig S, Johnson S, Bonvini E (2010) Therapeutic control of B cell activation via recruitment of Fcgamma receptor IIb (CD32B) inhibitory function with a novel bispecific antibody scaffold. Arthritis Rheum 62(7):1933–1943

    CAS  PubMed  Google Scholar 

  • Völkel T, Korn T, Bach M, Müller R, Kontermann RE (2001) Optimized linker sequences for the expression of monomeric and dimeric bispecific single-chain diabodies. Protein Eng 14:815–823

    Article  PubMed  Google Scholar 

  • Whitlow M, Filpula D, Rollence ML, Feng S-L, Wood JF (1994) Multivalent Fvs: characterization of single-chain Fv oligomers and preparation of a bispecific Fv. Protein Eng 7:1017–1026

    Article  CAS  PubMed  Google Scholar 

  • Wu AM, Williams LE, Zieran L, Padma A, Sherman M, Bebb GG, Odom-MAryon T, Wong JYC, Shively JE, Raubitschek AA (1999) Anti-carcinoembryonic antigen (CEA) diabody for rapid tumor targeting and imaging. Tumor Target 4:47–58

    CAS  Google Scholar 

  • Xiong D, Xu Y, Liu H, Peng H, Shao X, Lai Z, Fan D, Yang M, Han J, Xie Y, Yang C, Zhu Z (2002) Efficient inhibition of human B-cell lymphoma xenografts with an anti-CD20 x anti-CD3 bispecific diabody. Cancer Lett 177(1):29–39

    Article  CAS  PubMed  Google Scholar 

  • Zhu Z, Zapata G, Shalaby R, Snedecor B, Chen H, Carter P (1996) High level secretion of a humanized bispecific diabody from Escherichia coli. Biotechnology 14(2):192–196

    Article  CAS  PubMed  Google Scholar 

  • Zhu Z, Presta LG, Zapata G, Carter P (1997) Remodeling domain interfaces to enhance heterodimer formation. Protein Sci 6:781–788

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Zellbiologie und Immunologie, Universität Stuttgart, Allmandring 31, 70569, Stuttgart, Germany

    Dafne Müller & Roland E. Kontermann

Authors
  1. Dafne Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roland E. Kontermann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dafne Müller .

Editor information

Editors and Affiliations

  1. Inst. Zellbiologie und Immunologie, Universität Stuttgart, Allmandring 31, Stuttgart, 70569, Germany

    Roland E. Kontermann

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Müller, D., Kontermann, R.E. (2011). Diabodies, Single-Chain Diabodies, and Their Derivatives. In: Kontermann, R. (eds) Bispecific Antibodies. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-20910-9_5

Download citation

Publish with us

Policies and ethics

Search

Navigation