Engineered hapten-binding antibody derivatives for modulation of pharmacokinetic properties of small molecules and targeted payload delivery

Immunological Reviews

Volumn 270, Issue 1, 2016, Pages 165-177

  Dengl, Stefan ^a   Sustmann, Claudio ^a   Brinkmann, Ulrich ^a  

^a ROCHE INNOVATION CENTER MUNICH   (Germany)

Author keywords

Biotin; Digoxigenin; Protein engineering; Protein structure; Targeted therapy

Indexed keywords

BISPECIFIC ANTIBODY; HAPTEN ANTIBODY; HAPTEN BINDING ANTIBODY; IMMUNOGLOBULIN G; REAGENT; UNCLASSIFIED DRUG; BIOLOGICAL MARKER; HAPTEN; HYBRID PROTEIN; MEMBRANE ANTIGEN; PROTEIN BINDING;

ANTIBODY ENGINEERING; ANTIBODY STRUCTURE; ANTIGEN BINDING; COVALENT BOND; IMMUNOMODULATION; PRIORITY JOURNAL; REVIEW; ANIMAL; CHEMISTRY; DRUG DELIVERY SYSTEM; HUMAN; IMMUNOLOGY; METABOLISM; MOLECULARLY TARGETED THERAPY; PROTEIN ENGINEERING;

ANIMALS; ANTIBODIES, BISPECIFIC; ANTIGENS, SURFACE; BIOMARKERS; DRUG DELIVERY SYSTEMS; HAPTENS; HUMANS; IMMUNOGLOBULIN G; MOLECULAR TARGETED THERAPY; PROTEIN BINDING; PROTEIN ENGINEERING; RECOMBINANT FUSION PROTEINS;

EID: 84957709906     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/imr.12386     Document Type: Review

References (76)

1. Poljak RJ, Amziel LM, Avey HP, Chen BL, Phizackerley RP, Saul F. Three-dimensional structure of the Fab' fragment of a human immunoglobulin at 2.8-A resolution. Proc Natl Acad Sci USA 1973;70:3305-3310.
2. Amzel LM, Poljak RJ, Saul F, Varga JM, Richards FF. The three dimensional structure of a combining region-ligand complex of immunoglobulin NEW at 3.5-A resolution. Proc Natl Acad Sci USA 1974;71:1427-1430.
3. Padlan EA, Segal DM, Spande TF, Davies DR, Rudikoff S, Potter M. Structure at 4.5 Å resolution of a phosphorylcholine-binding fab. Nat New Biol 1973;245:165-167.
4. Segal DM, Padlan EA, Cohen GH, Rudikoff S, Potter M, Davies DR. The three-dimensional structure of a phosphorylcholine-binding mouse immunoglobulin Fab and the nature of the antigen binding site. Proc Natl Acad Sci USA 1974;71:4298-4302.
5. Kabat EA. Proceedings. The structural basis of antibody specificity. Hoppe-Seyler's Z Physiol Chem 1976;357:613-614.
6. Padlan EA. Structural implications of sequence variability in immunoglobulins. Proc Natl Acad Sci USA 1977;74:2551-2555.
7. Padlan EA, Kabat EA. Modeling of antibody combining sites. Methods Enzymol 1991;203:3-21.
8. Plueckthun A. Antibody engineering. Curr Opin Biotechnol 1991;2:238-246.
9. Carter P, et al. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci USA 1992;89:4285-4289.
10. Kabat EA, Wu TT, Perry HM, Gottesman KS, Foeller C. Sequences of Proteins of immunological interest. National Institutes of Health Publication No 91-3242. Bethesda, MD: National Institutes of Health, 1991.
11. Bird RE, et al. Single-chain antigen-binding proteins. Science 1988;242:423-426.
12. Skerra A. Plueckthun A Assembly of a functional immunoglobulin Fv fragment in Escherichia coli. Science 1988;240:1038-1041.
13. Barbas CF 3rd, Kang AS, Lerner RA, Benkovic SJ. Assembly of combinatorial antibody libraries on phage surfaces: the gene III site. Proc Natl Acad Sci USA 1991;88:7978-7982.
14. Little M, Breitling F, Duebel S, Fuchs P, Braunagel M. Human antibody libraries in Escherichia coli. J Biotechnol 1995;41:187-195.
15. Boder ET, Midelfort KS, Wittrup KD. Directed evolution of antibody fragments with monovalent femtomolar antigen-binding affinity. Proc Natl Acad Sci USA 2000;97:10701-10705.
16. Thie H, Voedisch B, Dübel S, Hust M, Schirrmann T. Affinity maturation by phage display. Methods Mol Biol 2009;525:309-322.
17. Glockshuber R, Schmidt T, Plueckthun A. The disulfide bonds in antibody variable domains: effects on stability, folding in vitro, and functional expression in Escherichia coli. Biochemistry 1992;31:1270-1279.
18. Berman HM, et al. The protein data bank. Nucleic Acids Res 2000;28:235-242.
19. Singh MK, Srivastava S, Raghava GP, Varshney GC, Hapten DB. A comprehensive database of haptens, carrier proteins and anti-hapten antibodies. Bioinformatics 2006;22:253-255.
20. Kessler C. The digoxigenin:anti-digoxigenin (DIG) technology - a survey on the concept and realization of a novel bioanalytical indicator system. Mol Cell Probes 1991;5:161-205.
21. Holtke HJ, et al. The digoxigenin (DIG) system for non-radioactive labelling and detection of nucleic acids - an overview. Cell Mol Biol 1995;41:883-905.
22. Dengl S, et al. Hapten-directed spontaneous disulfide shuffling: a universal technology for site-directed covalent coupling of payloads to antibodies. FASEB J 2015;29:1763-1779.
23. Grote M, Haas AK, Klein C, Schaefer W, Brinkmann U. Bispecific antibody derivatives based on full-length IgG formats. Methods Mol Biol 2012;901:247-263.
24. Croasdale R, et al. Development of tetravalent IgG1 dual targeting IGF-1R-EGFR antibodies with potent tumor inhibition. Arch Biochem Biophys 2012;526:206-218.
25. Schanzer J, et al. Development of tetravalent, bispecific CCR5 antibodies with antiviral activity against CCR5 monoclonal antibody-resistant HIV-1 strains. Antimicrob Agents Chemother 2011;55:2369-2378.
26. Schanzer JM, et al. A novel glycoenginereed bispecific antibody format for targeted inhibition of EGFR and IGF-1R demonstrating unique molecular properties. J Biol Chem 2014;289:18693-18706.
27. Haas AK, von Schwerin C, Matscheko D, Brinkmann U. Fluorescent citrine-IgG fusion proteins produced in mammalian cells. mAbs 2010;2:648-661.
28. Kontermann RE, Brinkmann U. Bispecific antibodies. Drug Discovery Today 2015;20:838-847.
29. Weidle UH, Tiefenthaler G, Weiss EH, Georges G, Brinkmann U. The intriguing options of multispecific antibody formats for treatment of cancer. Cancer Genomics Proteomics 2013;10:1-18.
30. Weidle UH, Kontermann RE, Brinkmann U. Tumor-antigen-binding bispecific antibodies for cancer treatment. Semin Oncol 2014;41:653-660.
31. Coloma MJ, Morrison SL. Design and production of novel tetravalent bispecific antibodies. Nat Biotechnol 1997;15:159-163.
32. Brinkmann U, Reiter Y, Jung SH, Lee B, Pastan I. A recombinant immunotoxin containing a disulfide-stabilized Fv fragment. Proc Natl Acad Sci USA 1993;90:7538-7542.
33. Reiter Y, Brinkmann U, Webber KO, Jung SH, Lee B, Pastan I. Engineering interchain disulfide bonds into conserved framework regions of Fv fragments: improved biochemical characteristics of recombinant immunotoxins containing disulfide-stabilized Fv. Protein Eng 1994;7:697-704.
34. Reiter Y, Brinkmann U, Jung SH, Pastan I, Lee B. Disulfide stabilization of antibody Fv: computer predictions and experimental evaluation. Protein Eng 1995;8:1323-1331.
35. Reiter Y, Brinkmann U, Lee B, Pastan I. Engineering antibody Fv fragments for cancer detection and therapy: disulfide-stabilized Fv fragments. Nat Biotechnol 1996;14:1239-1245.
36. Rodrigues ML, et al. Development of a humanized disulfide-stabilized anti-p185HER2 Fv-beta-lactamase fusion protein for activation of a cephalosporin doxorubicin prodrug. Cancer Res 1995;55:63-70.
37. Reiter Y, et al. Improved binding and antitumor activity of a recombinant anti-erbB2 immunotoxin by disulfide stabilization of the Fv fragment. J Biol Chem 1994;269:18327-18331.
38. Reiter Y, Kreitman RJ, Brinkmann U, Pastan I. Cytotoxic and antitumor activity of a recombinant immunotoxin composed of disulfide-stabilized anti-Tac Fv fragment and truncated Pseudomonas exotoxin. Int J Cancer 1994;58:142-149.
39. Reiter Y, Pai LH, Brinkmann U, Wang QC, Pastan I. Antitumor activity and pharmacokinetics in mice of a recombinant immunotoxin containing a disulfide-stabilized Fv fragment. Cancer Res 1994;54:2714-2718.
40. Reiter Y, Brinkmann U, Kreitman RJ, Jung SH, Lee B, Pastan I. Stabilization of the Fv fragments in recombinant immunotoxins by disulfide bonds engineered into conserved framework regions. Biochemistry 1994;33:5451-5459.
41. Webber KO, Reiter Y, Brinkmann U, Kreitman R, Pastan I. Preparation and characterization of a disulfide-stabilized Fv fragment of the anti-Tac antibody: comparison with its single-chain analog. Mol Immunol 1995;32:249-258.
42. Bera TK, Onda M, Brinkmann U, Pastan I. A bivalent disulfide-stabilized Fv with improved antigen binding to erbB2. J Mol Biol 1998;281:475-483.
43. Brinkmann U, Chowdhury PS, Roscoe DM, Pastan I. Phage display of disulfide-stabilized Fv fragments. J Immunol Methods 1995;182:41-50.
44. Metz S, et al. Bispecific digoxigenin-binding antibodies for targeted payload delivery. Proc Natl Acad Sci USA 2011;108:8194-8199.
45. Metz S, et al. Bispecific antibody derivatives with restricted binding functionalities that are activated by proteolytic processing. Protein Eng Des Sel 2012;25:571-580.
46. Ridgway JB, Presta LG, Carter P. 'Knobs-into-holes' engineering of antibody CH3 domains for heavy chain heterodimerization. Protein Eng 1996;9:617-621.
47. Merchant AM, et al. An efficient route to human bispecific IgG. Nat Biotechnol 1998;16:677-681.
48. Wu C, et al. Molecular construction and optimization of anti-human IL-1alpha/beta dual variable domain immunoglobulin (DVD-Ig) molecules. mAbs 2009;1:339-347.
49. Wu C, et al. Simultaneous targeting of multiple disease mediators by a dual-variable-domain immunoglobulin. Nat Biotechnol 2007;25:1290-1297.
50. Gu J, Ghayur T. Generation of dual-variable-domain immunoglobulin molecules for dual-specific targeting. Methods Enzymol 2012;502:25-41.
51. Schaefer W, et al. Immunoglobulin domain crossover as a generic approach for the production of bispecific IgG antibodies. Proc Natl Acad Sci USA 2011;108:11187-11192.
52. Klein C, et al. Progress in overcoming the chain association issue in bispecific heterodimeric IgG antibodies. mAbs 2012;4:653-663.
53. Kontermann RE. Strategies for extended serum half-life of protein therapeutics. Curr Opin Biotechnol 2011;22:868-876.
54. Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 2007;7:715-725.
55. Hutt M, Färber-Schwarz A, Unverdorben F, Richter F, Kontermann RE. Plasma half-life extension of small recombinant antibodies by fusion to immunoglobulin-binding domains. J Biol Chem 2012;287:4462-4469.
56. Pasut G, Veronese FM. State of the art in PEGylation: the great versatility achieved after forty years of research. J Control Release 2012;161:461-472.
57. Antonelli M, Sandroni C. Hydroxyethyl starch for intravenous volume replacement: more harm than benefit. JAMA 2013;309:723-724.
58. Junutula JR, et al. Site specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat Biotechnol 2008;26:925-932.
59. Panowksi S, Bhakta S, Raab H, Polakis P, Junutula JR. Site-specific antibody drug conjugates for cancer therapy. mAbs 2014;6:34-45.
60. Doppalapudi VR, et al. Chemical generation of bispecific antibodies. Proc Natl Acad Sci USA 2010;107:22611-22616.
61. Doppalapudi VR, et al. Chemically programmed antibodies: endothelin receptor targeting CovX-Bodies Bioorg. Med Chem Lett 2007;17:501-506.
62. Zac-Varghese S, De Silva A, Bloom SR. Translational studies on PYY as a novel target in obesity. Curr Opin Pharmacol 2011;11:582-585.
63. Hoffmann E, et al. PK modulation of haptenylated peptides via non-covalent antibody complexation. J Controlled Release 2013;171:48-56.
64. Schneider B, et al. Targeted siRNA delivery and mRNA knockdown mediated by bispecific digoxigenin-binding antibodies. Mol Ther Nucleic Acids 2012;1:e46.
65. Thorey IS, Grote M, Mayer K, Brinkmann U. Hapten-binding bispecific antibodies for the targeted delivery of siRNA and siRNA-containing nanoparticles. Methods Mol Biol (Clifton, N.J.) 2016;1364:219-234.
66. Rozema DB, et al. Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes. Proc Natl Acad Sci USA 2007;104:12982-12987.
67. Frank-Kamenetsky M, et al. Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc Natl Acad Sci USA 2008;105:11915-11920.
68. Tung HY, et al. Selective delivery of PEGylated compounds to tumor cells by anti-PEG hybrid antibodies. Mol Cancer Ther 2015;14:1317-1326.
69. Kao CH, et al. One-step mixing with humanized anti-mPEG bispecific antibody enhances tumor accumulation and therapeutic efficacy of mPEGylated nanoparticles. Biomaterials 2014;35:9930-9940.
70. Goldenberg DM, Chang CH, Rossi EA, McBride JW, Sharkey RM. Pretargeted molecular imaging and radioimmunotherapy. Theranostics 2012;2:523-540.
71. van de Watering FC, Rijpkema M, Perk L, Brinkmann U, Oyen WJ, Boerman OC. Zirconium-89 labeled antibodies: a new tool for molecular imaging in cancer patients. BioMed Res Int 2014;2014:203601.
72. Aarts F, et al. Pretargeted radioimmunoscintigraphy in patients with primary colorectal cancer using a bispecific anticarcinoembryonic antigen CEA X anti-di-diethylenetriaminepentaacetic acid F(ab')2 antibody. Cancer 2010;116(Suppl):1111-1117.
73. Kraeber-Bodere F, et al. A pretargeting system for tumor PET imaging and radioimmunotherapy. Front Pharmacol 2015;6:54.
74. Panke C, et al. Quantification of cell surface proteins with bispecific antibodies. Protein Eng Des Sel 2013;26:645-654.
75. Schwartz A, Gaigalas AK, Wang L, Marti GE, Vogt RF, Fernandez-Repollet E. Formalization of the MESF unit of fluorescence intensity. Cytometry B Clin Cytom 2004;57:1-6.
76. Lenkei R, et al. Performance of calibration standards for antigen quantitation with flow cytometry. Cytometry 1998;33:188-196.