The current status and prospects of antibody engineering for therapeutic use: Focus on glycoengineering technology

Journal of Pharmaceutical Sciences

Volumn 104, Issue 3, 2015, Pages 930-941

  Niwa, Rinpei ^a   Satoh, Mitsuo ^a  

^a KYOWA HAKKO KOGYO CO LTD   (Japan)

Author keywords

Biotechnology; Cancer; Conjugation; Glycosylation; Immunology; Immunotherapy; Targeted drug delivery; Therapeutic antibody

Indexed keywords

BISPECIFIC ANTIBODY; DEFUCOSYLATED ANTIBODY; DRUG ANTIBODY; FC RECEPTOR; FUCOSE; GLYCOENGINEERED ANTIBODY; MEMBRANE ANTIGEN; MOGAMULIZUMAB; MONOCLONAL ANTIBODY; OBINUTUZUMAB; OLIGOSACCHARIDE; RITUXIMAB; TRASTUZUMAB; UNCLASSIFIED DRUG; ANTIBODY CONJUGATE;

AMINO ACID SEQUENCE; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTIBODY ENGINEERING; CLINICAL TRIAL (TOPIC); COMPLEMENT DEPENDENT CYTOTOXICITY; CROHN DISEASE; DRUG ACTIVITY; DRUG CONJUGATION; DRUG DESIGN; DRUG HALF LIFE; DRUG MANUFACTURE; DRUG MECHANISM; DRUG STRUCTURE; DRUG SYNTHESIS; FUCOSYLATION; GLYCOSYLATION; HUMAN; MAJOR HISTOCOMPATIBILITY COMPLEX; MALIGNANT NEOPLASTIC DISEASE; MOLECULAR MECHANICS; NATURAL KILLER CELL MEDIATED CYTOTOXICITY; NONHUMAN; PHASE 3 CLINICAL TRIAL (TOPIC); REVIEW; RHEUMATOID ARTHRITIS; ANTIBODY SPECIFICITY; BIOSYNTHESIS; CHEMISTRY; IMMUNOTHERAPY; METABOLISM; PHARMACEUTICS; PROCEDURES; PROTEIN CONFORMATION; PROTEIN ENGINEERING; PROTEIN PROCESSING; STRUCTURE ACTIVITY RELATION;

ANTIBODIES, BISPECIFIC; ANTIBODIES, MONOCLONAL; ANTIBODY SPECIFICITY; GLYCOSYLATION; IMMUNOCONJUGATES; IMMUNOTHERAPY; PROTEIN CONFORMATION; PROTEIN ENGINEERING; PROTEIN PROCESSING, POST-TRANSLATIONAL; STRUCTURE-ACTIVITY RELATIONSHIP; TECHNOLOGY, PHARMACEUTICAL;

EID: 84922807192     PISSN: 00223549     EISSN: 15206017     Source Type: Journal    
DOI: 10.1002/jps.24316     Document Type: Review

References (130)

1. Forero A, Lobuglio AF. 2003. History of antibody therapy for non-Hodgkin's lymphoma. Semin Oncol 30:1-5.
2. Grillo-Lopez AJ. 2003. Rituximab (Rituxan/MabThera): The first decade (1993-2003). Expert Rev Anticancer Ther 3:767-769.
3. Vogel CL, Franco SX. 2003. Clinical experience with trastuzumab (herceptin). Breast J 9:452-462.
4. de Bono JS, Rowinsky EK. 2002. The ErbB receptor family: A therapeutic target for cancer. Trends Mol Med 8:S19-S26.
5. Olsen NJ, Stein CM. 2004. New drugs for rheumatoid arthritis. N Engl J Med 350:2167-2179.
6. Junghans RP, Anderson CL. 1996. The protection receptor for IgG catabolism is the beta2-microglobulin-containing neonatal intestinal transport receptor. Proc Natl Acad Sci USA 93:5512-5516.
7. Gallinger S, Reilly RM, Kirsh JC, Odze RD, Schmocker BJ, Hay K, Polihronis J, Damani MT, Shpitz B, Stern HS. 1993. Comparative dual label study of first and second generation antitumor-associated glycoprotein-72 monoclonal antibodies in colorectal cancer patients. Cancer Res 53:271-278.
8. Scheinberg DA, Chapman PB. 1995. Therapeutic applications of monoclonal antibodies for human disease. In Monoclonal antibodies: Principles and applications; Birch JR, Lennox ES, Eds. New York: Wiley-Liss, pp 45-105.
9. Brüggemann M,Williams GT, Bindon CI, Clark MR,Walker MR, Jefferis R, Waldmann H, Neuberger MS. 1987. Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies. J Exp Med 166:1351-1361.
10. Schumaker VN, Calcott MA, Spiegelberg HL,Müller-Eberhard HJ.1976. Ultracentifuge studies of the binding of IgG of different subclasses to the Clq subunit of the first component of complement. Biochemistry 15:5175-5181.
11. Roopenian DC, Christianson GJ, Sproule TJ, Brown AC, Akilesh S, Jung N, Petkova S, Avanessian L, Choi EY, Shaffer DJ, Eden PA, Anderson CL. 2003. The MHC class I-like IgG receptor controls perinatal IgG transport, IgG homeostasis, and fate of IgG-Fc-coupled drugs. J Immunol 170:3528-3533.
12. Roopenian DC, Shreeram A. 2007. FcRn: The neonatal Fc receptor comes of age. Nat Rev Immunol 7:715-725.
13. Clark MR. 1997. IgG effector mechanisms. Chem Immunol 65:88-110.
14. Morgan A, Jones ND, Nesbitt AM, Chaplin L, Bodmer MW, Emtage JS. 1995. The N-terminal end of the CH2 domain of chimeric human IgG1 anti-HLA-DR is necessary for C1q, Fc gamma RI and Fc gamma RIII binding. Immunology 86:319-324.
15. Jefferis R, Lund J. 2002. Interaction sites on human IgG-Fc for FcgammaR: Current models. Immunol Lett 82:57-65.
16. Walker MR, Lund J, Thompson KM, Jefferis R. 1989. Aglycosylation of human IgG1 and IgG3 monoclonal antibodies can eliminate recognition by human cells expressing Fc gamma RI and/or Fc gamma RII receptors. Biochem J 259:347-353.
17. Tao MH, Morrison SL. 1989. Studies of aglycosylated chimeric mouse-human IgG. Role of carbohydrate in the structure and effector functions mediated by the human IgG constant region. J Immunol 143:2595-2601.
18. Krapp S, Mimura Y, Jefferis R, Huber R, Sondermann P. 2003.Structural analysis of human IgG-Fc glycoforms reveals a correlation between glycosylation and structural integrity. J Mol Biol 325:979-989.
19. Walker MR, Lund J, Thompson KM, Jefferis R. 1989. Aglycosylation of human IgG1 and IgG3 monoclonal antibodies can eliminate recognition by human cells expressing Fc gamma RI and/or Fc gamma RII receptors. Biochem J 259:347-353.
20. Huber R, Deisenhofer J, Colman PM, Matsushima M, Palm W.1976. Crystallographic structure studies of an IgG molecule and an Fc fragment. Nature 264:415-420.
21. Radaev S, Motyka S, Fridman WH, Sautes-Fridman C, Sun PD.2001. The structure of a human type III Fcgamma receptor in complex with Fc. J Biol Chem 276:16469-16477.
22. Harris LJ, Skaletsky E, McPherson A. 1998. Crystallographic structure of an intact IgG1 monoclonal antibody. J Mol Biol 275:861-872.
23. Mizuochi T, Taniguchi T, Shimizu A, Kobata A. 1982. Structural and numerical variations of the carbohydrate moiety of immunoglobulin G. J Immunol 129:2016-2020.
24. Harada H, Kamei M, Tokumoto Y, Yui S, Koyama F, Kochibe N, Endo T, Kobata A. 1987. Systematic fractionation of oligosaccharides of human immunoglobulin G by serial affinity chromatography on immobilized lectin columns. Anal Biochem 164:374-381.
25. Rudd PM, Leatherbarrow RJ, Rademacher TW, Dwek RA. 1991.Diversification of the IgG molecule by oligosaccharides. Mol Immunol 28:1369-1378.
26. Scallon BJ, Tam SH, McCarthy SG, Cai AN, Raju TS. 2007. Higher levels of sialylated Fc glycans in immunoglobulin G molecules can adversely impact functionality. Mol Immunol 44:1524-1534.
27. Kumpel BM, Rademacher TW, Rook GA, Williams PJ, Wilson IB.1994. Galactosylation of human IgG monoclonal anti-D produced by EBV-transformed B-lymphoblastoid cell lines is dependent on culture method and affects Fc receptor-mediated functional activity. Hum Antibodies Hybridomas 5:143-151.
28. Umaña P, Jean-Mairet J, Moudry R, Amstutz H, Bailey JE. 1999.Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity. Nat Biotechnol 17:176-180.
29. Yu M, Brown D, Reed C, Chung S, Lutman J, Stefanich E, Wong A, Stephan JP, Bayer R. 2012. Production, characterization, and pharmacokinetic properties of antibodies with N-linked mannose-5 glycans. MAbs 24:475-487.
30. Kanda Y, Yamada T, Mori K, Okazaki A, Inoue M, Kitajima-Miyama K, Kuni-Kamochi R, Nakano R, Yano K, Kakita S, Shitara K, Satoh M. 2007. Comparison of biological activity among nonfucosylated therapeutic IgG1 antibodies with three different N-linked Fc oligosaccharides: The high-mannose, hybrid, and complex types. Glycobiology 17:104-118.
31. Raju TS. 2008. Terminal sugars of Fc glycans influence antibody effector functions of IgGs. Curr Opin Immunol 20:471-478.
32. Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. 2008. Tumor necrosis factor antagonist mechanisms of action: A comprehensive review. Pharmacol Ther 117:244-279.
33. Shih T, Lindley C. 2006. Bevacizumab: An angiogenesis inhibitor for the treatment of solid malignancies. Clin Ther 28:1779-1802.
34. Braghiroli MI, Sabbaga J, Hoff PM. 2012. Bevacizumab: Overview of the literature. Expert Rev Anticancer Ther 12:567-580.
35. Cartron G, Dacheux L, Salles G, Solal-Celigny P, Bardos P, Colombat P, Watier H. 2002. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood 99:754-758.
36. Dall'Ozzo S, Tartas S, Paintaud G, Cartron G, Colombat P, Bardos P, Watier H, Thibault G. 2004. Rituximab-dependent cytotoxicity by natural killer cells: Influence of FCGR3A polymorphism on the concentration-effect relationship. Cancer Res 64:4664-4669.
37. Anolik JH, Campbell D, Felgar RE, Young F, Sanz I, Rosenblatt J, Looney RJ. 2003. The relationship of FcgammaRIIIa genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus. Arthritis Rheum 48:455-459.
38. Weng WK, Levy R. 2003. Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol 21:3940-3947.
39. Musolino A, Naldi N, Bortesi B, Pezzuolo D, Capelletti M, Missale G, Laccabue D, Zerbini A, Camisa R, Bisagni G, Neri TM, Ardizzoni A. 2008. Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J Clin Oncol 26:1789-1796.
40. Kennedy AD, Beum PV, Solga MD, DiLillo DJ, Lindorfer MA, Hess CE, Densmore JJ, Williams ME, Taylor RP. 2004. Rituximab infusion promotes rapid complement depletion and acute CD20 loss in chronic lymphocytic leukemia. J Immunol 172:3280-3288.
41. Coiffier B, Lepretre S, Pedersen LM, Gadeberg O, Fredriksen H, van Oers MH, Wooldridge J, Kloczko J, Holowiecki J, Hellmann A, Walewski J, Flensburg M, Petersen J, Robak T. 2008. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: A phase 1-2 study. Blood 111:1094-1100.
42. Mizuochi T, Taniguchi T, Shimizu A, Kobata A. 1982. Structural and numerical variations of the carbohydrate moiety of immunoglobulin G. J Immunol 129:2016-2020.
43. Harada H, Kamei M, Tokumoto Y, Yui S, Koyama F, Kochibe N, Endo T, Kobata A. 1987. Systematic fractionation of oligosaccharides of human immunoglobulin G by serial affinity chromatography on immobilized lectin columns. Anal Biochem 164:374-381.
44. Shields RL, Lai J,Keck R, O'Connell LY, Hong K, Meng YG,Weikert SH, Presta LG. 2002. Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human Fcgamma RIII and antibodydependent cellular toxicity. J Biol Chem 277:26733-26740.
45. Shinkawa T, Nakamura K, Yamane N, Shoji-Hosaka E, Kanda Y, Sakurada M, Uchida K, Anazawa H, Satoh M, Yamasaki M, Hanai N, Shitara K. 2003. The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity. J Biol Chem 278:3466-3473.
46. Niwa R, Shoji-Hosaka E, Sakurada M, Shinkawa T, Uchida K, Nakamura K, Matsushima K, Ueda R, Hanai N, Shitara K. 2004. Defucosylated chimeric anti-CC chemokine receptor 4 IgG1 with enhanced antibody-dependent cellular cytotoxicity shows potent therapeutic activity to T-cell leukemia and lymphoma. Cancer Res 64:2127-2133.
47. Yamane-Ohnuki N, Kinoshita S, Inoue-Urakubo M, Kusunoki M, Iida S, Nakano R,Wakitani M, Niwa R, Sakurada M, Uchida K, Shitara K, Satoh M. 2004. Establishment of FUT8 knockout Chinese hamster ovary cells: An ideal host cell line for producing completely defucosylated antibodies with enhanced antibody-dependent cellular cytotoxicity. Biotechnol Bioeng 87:614-622.
48. Ferrara C, Brunker P, Suter T, Moser S, Puntener U, Umana P.2006. Modulation of therapeutic antibody effector functions by glycosylation engineering: Influence of Golgi enzyme localization domain and co-expression of heterologous $ 1, 4-N-acetylglucosaminyltransferase III and Golgi a-mannosidase II. Biotechnol Bioeng 93:851-861.
49. Li H, Sethuraman N, Stadheim TA, Zha D, Prinz B, Ballew N, Bobrowicz P, Choi BK, Cook WJ, Cukan M, Houston-Cummings NR, Davidson R, Gong B, Hamilton SR, Hoopes JP, Jiang Y, Kim N, Mansfield R, Nett JH, Rios S, Strawbridge R, Wildt S, Gerngross TU. 2006.Optimization of humanized IgGs in glycoengineered Pichia pastoris. Nat Biotechnol 24:210-215.
50. Cox KM, Sterling JD, Regan JT, Gasdaska JR, Frantz KK, Peele CG, Black A, Passmore D, Moldovan-Loomis C, Srinivasan M, Cuison S, Cardarelli PM, Dickey LF. 2006. Glycan optimization of a human monoclonal antibody in the aquatic plant Lemna minor. Nat Biotechnol 24:1591-1597.
51. Schuster M, Jost W, Mudde GC,Wiederkum S, Schwager C, Janzek E, Altmann F, Stadlmann J, Stemmer C, Gorr G. 2007. In vivo glycoengineered antibody with improved lytic potential produced by an innovative non-mammalian expression system. Biotechnol J 2:700-708.
52. Matsumiya S, Yamaguchi Y, Saito J, Nagano M, Sasakawa H, Otaki S, Satoh M, Shitara K, Kato K. 2007. Structural comparison of fucosylated and nonfucosylated Fc fragments of human immunoglobulin G1. J Mol Biol 368:767-779.
53. Oganesyan V, Damschroder MM, Leach W, Wu H, Dall'Acqua WF.2008. Structural characterization of a mutated, ADCC-enhanced human Fc fragment. Mol Immunol 45:1872-1882.
54. Ferrara C, Grau S, Jäger C, Sondermann P, Brünker P,Waldhauer I, Hennig M, Ruf A, Rufer AC, Stihle M, Umaña P, Benz J. 2011. Unique carbohydrate-carbohydrate interactions are required for high affinity binding between FcgammaRIII and antibodies lacking core fucose. Proc Natl Acad Sci USA 108:12669-12674.
55. Mizushima T, Yagi H, Takemoto E, Shibata-Koyama M, Isoda Y, Iida S, Masuda K, Satoh M, Kato K. 2011. Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans. Genes Cells 16:1071-1080.
56. Niwa R, Sakurada M,Kobayashi Y, Uehara A, Matsushima K, Ueda R, Nakamura K, Shitara K. 2005. Enhanced natural killer cell binding and activation by low-fucose IgG1 antibody results in potent antibodydependent cellular cytotoxicity induction at lower antigen density. Clin Cancer Res 11:2327-2336.
57. Vugmeyster Y, Howell K. 2004. Rituximab-mediated depletion of cynomolgus monkey B cells in vitro in different matrices: Possible inhibitory effect of IgG. Int Immunopharmacol 24:1117-1124.
58. Preithner S, Elm S, Lippold S, Locher M, Wolf A, da Silva AJ, Baeuerle PA, Prang NS. 2006. High concentrations of therapeutic IgG1 antibodies are needed to compensate for inhibition of antibodydependent cellular cytotoxicity by excess endogenous immunoglobulin G. Mol Immunol 43:1183-1193.
59. Iida S, Misaka H, Inoue M, Shibata M, Nakano R, Yamane-Ohnuki N, Wakitani M, Yano K, Shitara K, Satoh M. 2006. Nonfucosylated therapeutic IgG1 antibody can evade the inhibitory effect of serum immunoglobulin G on antibody-dependent cellular cytotoxicity through its high binding to FcgammaRIIIa. Clin Cancer Res 12:2879-2887.
60. Shibata-Koyama M, Iida S, Misaka H, Mori K, Yano K, Shitara K, Satoh M. 2009. Nonfucosylated rituximab potentiates human neutrophil phagocytosis through its high binding for FcgammaRIIIb and MHC class II expression on the phagocytotic neutrophils. Exp Hematol 37:309-321.
61. King DJ, Turner A, Farnsworth AP, Adair JR, Owens RJ, Pedley RB, Baldock D, Proudfoot KA, Lawson AD, Beeley NR, Millar K, Millican TA, Boyce BA, Antoniw P, Mountain A, Begent RH, Yarranton GT.1994. Improved tumor targeting with chemically cross-linked recombinant antibody fragments. Cancer Res 54:6176-6185.
62. Ghetie MA, Podar EM, Ilgen A, Gordon BE, Uhr JW, Vitetta ES. 1997. Homodimerization of tumor-reactive monoclonal antibodies markedly increases their ability to induce growth arrest or apoptosis of tumor cells. Proc Natl Acad Sci USA 94:7509-7514.
63. Ghetie MA, Bright H, Vitetta ES. 2001. Homodimers but not monomers of Rituxan (chimeric anti-CD20) induce apoptosis in human B-lymphoma cells and synergize with a chemotherapeutic agent and an immunotoxin. Blood 97:1392-1398.
64. Nakagawa T, Natsume A, Satoh M, Niwa R. 2010. Nonfucosylated anti-CD20 antibody potentially induces apoptosis in lymphoma cells through enhanced interaction with FcgammaRIIIb on neutrophils. Leuk Res 34:666-671.
65. Dhodapkar KM, Krasovsky J,Williamson B, Dhodapkar MV. 2002.Antitumor monoclonal antibodies enhance cross-presentation of cellular antigens and the generation of myeloma-specific killer T cells by dendritic cells. J Exp Med 195:125-133.
66. Harbers SO1, Crocker A, Catalano G, D'Agati V, Jung S, Desai DD, Clynes R. 2007. Antibody-enhanced cross-presentation of self antigen breaks T cell tolerance. J Clin Invest 117:1361-1369.
67. Abès R, Gélizé E, Fridman WH, Teillaud JL. 2010. Long-lasting antitumor protection by anti-CD20 antibody through cellular immune response. Blood 116:926-934.
68. Taylor C, Hershman D, Shah N, Suciu-Foca N, Petrylak DP, Taub R, Vahdat L, Cheng B, Pegram M, Knutson KL, Clynes R. 2007. Augmented HER-2 specific immunity during treatment with trastuzumab and chemotherapy. Clin Cancer Res 13:5133-5143.
69. Ferris RL, Jaffee EM, Ferrone S. 2010. Tumor antigen-targeted, monoclonal antibody-based immunotherapy: Clinical response, cellular immunity, and immunoescape. J Clin Oncol 28:4390-4399.
70. Ridgway JB, Presta LG, Carter P. 1996. 'Knobs-into-holes' engineering of antibody CH3 domains for heavy chain heterodimerization. Protein Eng 9:617-621.
71. Merchant AM, Zhu Z, Yuan JQ, Goddard A, Adams CW, Presta LG, Carter P. 1998. An efficient route to human bispecific IgG. Nat Biotechnol 1:677-681.
72. Bokemeyer C. 2010. Catumaxomab-trifunctional anti-EpCAM antibody used to treat malignant ascites. Expert Opin Biol Ther 10:1259-1269.
73. Ott MG, Marmé F, Moldenhauer G, Lindhofer H, Hennig M, Spannagl R, Essing MM, Linke R, Seimetz D. 2012. Humoral response to catumaxomab correlates with clinical outcome: Results of the pivotal phase II/III study in patients with malignant ascites. Int J Cancer 130:2195-2203.
74. Nagorsen D, Kufer P, Baeuerle PA, Bargou R. 2012. Blinatumomab: A historical perspective. Pharmacol Ther 136:334-342.
75. Topp MS, Goekbuget N, Stein AS, Bargou RC, Dombret H, Fielding AK, Ribera JM, Foà R, Zugmaier G, Holland C, Maniar T, Huber B, Nagorsen D, Kantarjian HM. 2014. Confirmatory open-label, singlearm, multicenter phase 2 study of the BiTE antibody blinatumomab in patients (pts) with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL). Annual Meeting of American Society of Clinical Oncology, Abstract 7005.
76. Brischwein K, Schlereth B, Guller B, Steiger C,Wolf A, Lutterbuese R, Offner S, Locher M, Urbig T, Raum T, Kleindienst P, Wimberger P, Kimmig R, Fichtner I, Kufer P, Hofmeister R, da Silva AJ, Baeuerle PA.2006. MT110: A novel bispecific single-chain antibody construct with high efficacy in eradicating established tumors. Mol Immunol 43:1129-1143.
77. Lutterbuese R, Raum T, Kischel R, Lutterbuese P, Schlereth B, Schaller E, Mangold S, Rau D, Meier P, Kiener PA, Mulgrew K, Oberst MD, Hammond SA, Baeuerle PA, Kufer P. 2009. Potent control of tumor growth by CEA/CD3-bispecific single-chain antibody constructs that are not competitively inhibited by soluble CEA. J Immunother 32:341-352.
78. Hoffmann P, Brandl C, Schuhmacher J, Mueller P, Finnern R, Fuergut M, Zopf D, Slootstra JW, Baeuerle PA, Rattel B, Kufer P. 2012. Regression of human prostate cancer xenografts in mice by AMG 212/BAY2010112, a novel PSMA/CD3-bispecific BiTE antibody crossreactive with non-human primate antigens. Mol Cancer Ther 11:2664-2673.
79. th Annual Meeting of American Society of Hematology, Abstract 360.
80. 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 Fvbased dual-affinity re-targeting protein leads to potent tumor cytolysis and in vivo B-cell depletion. J Mol Biol 399:436-449.
81. Kiewe P, Hasmüller S, Kahlert S, Heinrigs M, Rack B, Marm é A, Korfel A, Jäger M, Lindhofer H, Sommer H, Thiel E, Untch M. 2006. Phase I trial of the trifunctional anti-HER2 x anti-CD3 antibody ertumaxomab in metastatic breast cancer. Clin Cancer Res 12:3085-3091.
82. Sen M, Wankowski DM, Garlie NK, Siebenlist RE, Van Epps D, LeFever AV, Lum LG. 2001. 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 10:247-260.
83. Gall JM, Davol PA, Grabert RC, Deaver M, Lum LG. 2005. T cells armed with anti-CD3 x anti-CD20 bispecific antibody enhance killing of CD20+ malignant B cells and bypass complement-mediated rituximab resistance in vitro. Exp Hematol 33:452-459.
84. rd Annual Meeting of American Association of Cancer Research, Abstract 2319.
85. Huang S, Li C, Armstrong EA, Peet CR, Saker J, Amler LC, Sliwkowski MX, Harari PM. 2013. Dual targeting of EGFR and HER3 with MEHD7945A overcomes acquired resistance to EGFR inhibitors and radiation. Cancer Res 73:824-833.
86. McDonagh CF, Huhalov A, Harms BD, Adams S, Paragas V, Oyama S, Zhang B, Luus L, Overland R, Nguyen S, Gu J, Kohli N, Wallace M, Feldhaus MJ, Kudla AJ, Schoeberl B, Nielsen UB. 2012. Antitumor activity of a novel bispecific antibody that targets the ErbB2/ErbB3 oncogenic unit and inhibits heregulin-induced activation of ErbB3. Mol Cancer Ther 11:582-593.
87. Rao E, Li D, Underwood S, Mikol V, Davison M, Kruip J. 2012. Generation of a tetravalent bispecific antibody against IL4 and IL13 for the treatment of idiopathic pulmonary fibrosis. MAbs 4:14-16.
88. Erickson HK, Park PU, Widdison WC, Kovtun YV, Garrett LM, Hoffman K, Lutz RJ, Goldmacher VS, Blättler WA. 2006. Antibodymaytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res 66:4426-4433.
89. Doronina SO, Toki BE, Torgov MY, Mendelsohn BA, Cerveny CG, Chace DF, DeBlanc RL, Gearing RP, Bovee TD, Siegall CB, Francisco JA,Wahl AF, Meyer DL, Senter PD. 2003. Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat Biotechnol 21:778-784.
90. Hamann PR, Hinman LM, Beyer CF, Lindh D, Upeslacis J, Flowers DA, Bernstein I. 2002. An anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Choice of linker. Bioconjug Chem 13:40-46.
91. Erickson HK, Widdison WC, Mayo MF, Whiteman K, Audette C, Wilhelm SD, Singh R. 2010. Tumor delivery and in vivo processing of disulfide-linked and thioether-linked antibody-maytansinoid conjugates. Bioconjug Chem 21:84-92.
92. Kovtun YV, Goldmacher VS. 2007. Cell killing by antibody-drug conjugates. Cancer Lett 255:232-240.
93. Gerber HP, Koehn FE, Abraham RT. 2013. The antibody-drug conjugate: An enabling modality for natural product-based cancer therapeutics. Nat Prod Rep 30:625-639.
94. Junutula JR, Flagella KM, Graham RA, Parsons KL, Ha E, Raab H, Bhakta S, Nguyen T, Dugger DL, Li G, Mai E, Lewis Phillips GD, Hiraragi H, Fuji RN, Tibbitts J, Vandlen R, Spencer SD, Scheller RH, Polakis P, Sliwkowski MX. 2010. Engineered thio-trastuzumab-DM1 conjugate with an improved therapeutic index to target human epidermal growth factor receptor 2-positive breast cancer. Clin Cancer Res 16:4769-4778.
95. Junutula JR, Raab H, Clark S, Bhakta S, Leipold DD,Weir S, Chen Y, Simpson M, Tsai SP, Dennis MS, Lu Y, Meng YG, Ng C, Yang J, Lee CC, Duenas E, Gorrell J, Katta V, Kim A, McDorman K, Flagella K, Venook R, Ross S, Spencer SD, Lee Wong W, Lowman HB, Vandlen R, Sliwkowski MX, Scheller RH, Polakis P, Mallet W. 2008. Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat Biotechnol 26:925-932.
96. Tian F, Lu Y, Manibusan A, Sellers A, Tran H, Sun Y, Phuong T, Barnett R, Hehli B, Song F, DeGuzman MJ, Ensari S, Pinkstaff JK, Sullivan LM, Biroc SL, Cho H, Schultz PG, DiJoseph J, Dougher M,
97. Ma D, Dushin R, Leal M, Tchistiakova L, Feyfant E, Gerber HP, Sapra P. 2014. A general approach to site-specific antibody drug conjugates. Proc Natl Acad Sci USA 111:1766-1771.
98. Newland AM, Li JX, Wasco LE, Aziz MT, Lowe DK. 2013. Brentuximab vedotin: A CD30-directed antibody-cytotoxic drug conjugate. Pharmacotherapy 33:93-104.
99. Boyraz B, Sendur MA, Aksoy S, Babacan T, Roach EC, Kizilarslanoglu MC, Petekkaya I, Altundag K. 2013. Trastuzumab emtansine (T-DM1) for HER2-positive breast cancer. Curr Med Res Opin 29:405-414.
100. DiJoseph JF, Dougher MM, Kalyandrug LB, Armellino DC, Boghaert ER, Hamann PR, Moran JK, Damle NK. 2006. Antitumor efficacy of a combination of CMC-544 (inotuzumab ozogamicin), a CD22-targeted cytotoxic immunoconjugate of calicheamicin, and rituximab against non-Hodgkin's B-cell lymphoma. Clin Cancer Res 12:242-249.
101. Ikeda H, Hideshima T, Fulciniti M, Lutz RJ, Yasui H, Okawa Y, Kiziltepe T, Vallet S, Pozzi S, Santo L, Perrone G, Tai YT, Cirstea D, Raje NS, Uherek C, Dälken B, Aigner S, Osterroth F, Munshi N, Richardson P, Anderson KC. 2009. The monoclonal antibody nBT062 conjugated to cytotoxicMaytansinoids has selective cytotoxicity against CD138-positive multiple myeloma cells in vitro and in vivo. Clin Cancer Res 15:4028-4037.
102. Naumovski L, Junutula JR. 2010. Glembatumumab vedotin, a conjugate of an anti-glycoprotein non-metastatic melanoma protein B mAb and monomethyl auristatin E for the treatment of melanoma and breast cancer. Curr Opin Mol Ther 12:248-257.
103. Li D, Poon KA, Yu SF, Dere R, Go M, Lau J, Zheng B, Elkins K, Danilenko D, Kozak KR, Chan P, Chuh J, Shi X, Nazzal D, Fuh F, McBride J, Ramakrishnan V, de Tute R, Rawstron A, Jack AS, Deng R, Chu YW, Dornan D,Williams M, Ho W, Ebens A, Prabhu S, Polson AG. 2013. DCDT2980S, an anti-CD22-monomethyl auristatin E antibody-drug conjugate, is a potential treatment for non-Hodgkin lymphoma. Mol Cancer Ther 12:1255-1265.
104. Dornan D, Bennett F, Chen Y, Dennis M, Eaton D, Elkins K, French D, Go MA, Jack A, Junutula JR, Koeppen H, Lau J, McBride J, Rawstron A, Shi X, Yu N, Yu SF, Yue P, Zheng B, Ebens A, Polson AG. 2009. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood 114:2721-2729.
105. Sapra P, Stein R, Pickett J, Qu Z, Govindan SV, Cardillo TM, Hansen HJ, Horak ID, Griffiths GL, Goldenberg DM. 2005. Anti-CD74 antibody-doxorubicin conjugate, IMMU-110, in a human multiple myeloma xenograft and in monkeys. Clin Cancer Res 11:5257-5264.
106. th Annual Meeting of American Association of Cancer Research, Abstract LB-159.
107. Beck A, Reichert JM. 2012. Marketing approval of mogamulizumab: A triumph for glyco-engineering. MAbs 4:419-425.
108. Gagez AL, Cartron G. 2014. Obinutuzumab: A new class of anti-CD20 monoclonal antibody. Curr Opin Oncol 26(5):484-491.
109. Mössner E, Brünker P, Moser S, Püntener U, Schmidt C, Herter S, Grau R, Gerdes C, Nopora A, van Puijenbroek E, Ferrara C, Sondermann P, Jäger C, Strein P, Fertig G, Friess T, Schüll C, Bauer S, Dal Porto J, Del Nagro C, Dabbagh K, Dyer MJ, Poppema S, Klein C, Umaña P. 2010. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood 115:4393-4402.
110. Kolbeck R, Kozhich A, Koike M, Peng L, Andersson CK, Damschroder MM, Reed JL, Woods R, Dall'Acqua WW, Stephens GL, Erjefalt JS, Bjermer L, Humbles AA, Gossage D, Wu H, Kiener PA, Spitalny GL, Mackay CR, Molfino NA, Coyle AJ. 2010. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibodydependent cell-mediated cytotoxicity function. J Allergy Clin Immunol 125:1344-1353.
111. Herbst R, Wang Y, Gallagher S, Mittereder N, Kuta E, Damschroder M, Woods R, Rowe DC, Cheng L, Cook K, Evans K, Sims GP, Pfarr DS, Bowen MA, Dall'Acqua W, Shlomchik M, Tedder TF, Kiener P, Jallal B, Wu H, Coyle AJ. 2010. B-cell depletion in vitro and in vivo with an afucosylated anti-CD19 antibody. J Pharmacol Exp Ther 335:213-222.
112. Shields RL, Namenuk AK, Hong K, Meng YG, Rae J, Briggs J, Xie D, Lai J, Stadlen A, Li B, Fox JA, Presta LG. 2001. High resolution mapping of the binding site on human IgG1 for Fc(RI, Fc(RII, Fc(RIII, and FcRn and design of IgG1 variants with improved binding to the Fc(R. J Biol Chem 276:6591-6604.
113. Lazar GA, Dang W, Karki S, Vafa O, Peng JS, Hyun L, Chan C, Chung HS, Eivazi A, Yoder SC, Vielmetter J, Carmichael DF, Hayes RJ, Dahiyat BI. 2006. Engineered antibody Fc variants with enhanced effector function. Proc Natl Acad Sci USA 103:4005-4010.
114. Stavenhagen JB, Gorlatov S, Tuaillon N, Rankin CT, Li H, Burke S, Huang L, Vijh S, Johnson S, Bonvini E, Koenig S. 2007. Fc optimization of therapeutic antibodies enhances their ability to kill tumor cells in vitro and controls tumor expansion in vivo via low-affinity activating Fcgamma receptors. Cancer Res 67:8882-8890.
115. Vugmeyster Y, Beyer J, Howell K, Combs D, Fielder P, Yang J, Qureshi F, Sandlund B, Kawaguchi L, Dummer W, Lowman H, McKeever K. 2005. Depletion of B cells by a humanized anti-CD20 antibody PRO70769 in Macaca fascicularis. J Immunother 28:212-219.
116. Bowles JA, Wang SY, Link BK, Allan B, Beuerlein G, Campbell MA, Marquis D, Ondek B, Wooldridge JE, Smith BJ, Breitmeyer JB, Weiner GJ. 2006. Anti-CD20 monoclonal antibody with enhanced affinity for CD16 activates NK cells at lower concentrations and more effectively than rituximab. Blood 108:2648-2654.
117. Idusogie EE, Wong PY, Presta LG, Gazzano-Santoro H, Totpal K, Ultsch M, Mulkerrin MG. 2001. Engineered antibodies with increased activity to recruit complement. J Immunol 166:2571-2575.
118. Moore GL, Chen H, Karki S, Lazar GA. 2010. Engineered Fc variant antibodies with enhanced ability to recruit complement and mediate effector functions. MAbs 2:181-189.
119. Natsume A, In M, Takamura H, Nakagawa T, Shimizu Y, Kitajima K,Wakitani M, Ohta S, Satoh M, Shitara K, Niwa R. 2008. Engineered antibodies of IgG1/IgG3 mixed isotype with enhanced cytotoxic activities. Cancer Res 68:3863-3872.
120. Rudick R, Polman C, Clifford D, Miller D, Steinman L. 2013.Natalizumab: Bench to bedside and beyond. JAMA Neurol 70:172-182.
121. Nangia JR, Ma JD, Nguyen CM, Mendes MA, Trivedi MV. 2012.Denosumab for treatment of breast cancer bone metastases and beyond. Expert Opin Biol Ther 12:491-501.
122. Wang C, Thudium KB, Han M, Wang XT, Huang H, Feingersh D, Garcia C, Wu Y, Kuhne M, Srinivasan M, Singh S, Wong S, Garner N, Leblanc H, Bunch RT, Blanset D, Selby MJ, Korman AJ. 2014. In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol Res 2:846-856.
123. Aronson R, Gottlieb PA, Christiansen JS, Donner TW, Bosi E, Bode BW, Pozzilli P; DEFEND Investigator Group. 2014. Low-dose otelixizumab anti-CD3 monoclonal antibody DEFEND-1 study: Results of the randomized phase III study in recent-onset human type 1 diabetes. Diabetes Care 37:2746-2754.
124. An Z, Forrest G, Moore R, Cukan M, Haytko P, Huang L, Vitelli S, Zhao JZ, Lu P, Hua J, Gibson CR, Harvey BR, Montgomery D, Zaller D, Wang F, Strohl W. 2009. IgG2m4, an engineered antibody isotype with reduced Fc function. MAbs 1:572-579.
125. Hinton PR, Xiong JM, Johlfs MG, Tang MT, Keller S, Tsurushita N. 2006. An engineered human IgG1 antibody with longer serum halflife. J Immunol 176:346-356.
126. Dall'Acqua WF, Kiener PA, Wu H. 2006. Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). J Biol Chem 281:23514-23524.
127. Zalevsky J, Chamberlain AK, Horton HM, Karki S, Leung IW, Sproule TJ, Lazar GA, Roopenian DC, Desjarlais JR. 2010. Enhanced antibody half-life improves in vivo activity. Nat Biotechnol 28:157-159.
128. Farag SS, Flinn IW, Modali R, Lehman TA, Young D, Byrd JC.2004. Fc gamma RIIIa and Fc gamma RIIa polymorphisms do not predict response to rituximab in B-cell chronic lymphocytic leukemia. Blood 103:1472-1474.
129. Lin TS, Flinn IW, Modali R, Lehman TA, Webb J, Waymer S, Moran ME, Lucas MS, Farag SS, Byrd JC. 2005. FCGR3A and FCGR2A polymorphisms may not correlate with response to alemtuzumab in chronic lymphocytic leukemia. Blood 105:289-291.
130. Zhang W, Gordon M, Schultheis AM, Yang DY, Nagashima F, Azuma M, Chang HM, Borucka E, Lurje G, Sherrod AE, Iqbal S, Groshen S, Lenz HJ. 2007. FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with singleagent cetuximab. J Clin Oncol 25:3712-3718.