The continuous increase in the number of approved monoclonal antibody (mAb)-based therapy suggests that mAbs, and their derivatives, will continue to be the focus of the biotherapeutics industry for years to come. Although vast improvements in our capability to manufacture, characterize, and stabilize mAbs have been achieved, there are still challenges to be overcome. These include analytical and stabilization approaches associated with the development of high concentration mAb formulations. In addition, several mAb-based modalities are under development, including antibody drug conjugates (ADCs), fusion proteins, and bispecific antibodies (bsAbs), all designed to overcome the limitations encountered with mAb therapy. The current status of their development, with emphasis on manufacturing challenges as well as preliminary clinical results, will be reviewed.
References
[1]
Casadevall, A.; Scharff, M.D. Return to the past: The case for antibody-based therapies in infectious diseases. Clin. Infect. Dis. 1995, 21, 150–161, doi:10.1093/clinids/21.1.150.
Nadler, L.M.; Stashenko, P.; Hardy, R.; Kaplan, W.D.; Button, L.N.; Kufe, D.W.; Antman, K.H.; Schlossman, S.F. Serotherapy of a patient with a monoclonal antibody directed against a human lymphoma-associated antigen. Cancer Res. 1980, 40, 3147–3154.
[4]
Kohler, G.; Milstein, C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 1975, 256, 495–497, doi:10.1038/256495a0.
Marks, L. The birth pangs of monoclonal antibody therapeutics: The failure and legacy of Centoxin. MAbs 2012, 4, 403–412, doi:10.4161/mabs.19909.
[8]
Hurley, J.C. Sepsis management and antiendotoxin therapy after nebacumab. A reappraisal. Drugs 1994, 47, 855–861, doi:10.2165/00003495-199447060-00001.
[9]
Beck, A.; Wurch, T.; Bailly, C.; Corvaia, N. Strategies and challenges for the next generation of therapeutic antibodies. Nat. Rev. Immunol. 2010, 10, 345–352, doi:10.1038/nri2747.
[10]
Coiffier, B.; Lepage, E.; Brière, J.; Herbrecht, R.; Tilly, H.; Bouabdallah, R.; Morel, P.; Van Den Neste, E.; Salles, G.; Gaulard, P.; et al. CHOP chemotherapy plus rituximab compared with CHOPalone in elderly patients with diffuse large-B-cell lymphoma. N. Engl. J. Med. 2002, 346, 235–242, doi:10.1056/NEJMoa011795.
[11]
McLaughlin, P.; Grillo-López, A.J.; Link, B.K.; Levy, R.; Czuczman, M.S.; Williams, M.E.; Heyman, M.R.; Bence-Bruckler, I.; White, C.A.; Cabanillas, F.; et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: Half of patients respond to a four-dose treatment program. J. Clin. Oncol. 1998, 16, 2825–2833.
[12]
Reichert, J.M. Antibody-based therapeutics to watch in 2011. MAbs 2011, 3, 76–99, doi:10.4161/mabs.3.1.13895.
[13]
Sievers, E.L.; Appelbaum, F.R.; Spielberger, R.T.; Forman, S.J.; Flowers, D.; Smith, F.O.; Shannon-Dorcy, K.; Berger, M.S.; Bernstein, I.D. Selective ablation of acute myeloid leukemia using antibody-targeted chemotherapy: A phase I study of an anti-CD33 calicheamicin immunoconjugate. Blood 1999, 93, 3678–3684.
[14]
Weiner, L.M.; Surana, R.; Wang, S. Monoclonal antibodies: Versatile platforms for cancer immunotherapy. Nat. Rev. Immunol. 2010, 10, 317–327, doi:10.1038/nri2744.
[15]
Linke, R.; Klein, A.; Seimetz, D. Catumaxomab: Clinical development and future directions. MAbs 2010, 2, 129–136, doi:10.4161/mabs.2.2.11221.
[16]
Wang, W.; Singh, S.; Zeng, D.L.; King, K.; Nema, S. Antibody structure, instability, and formulation. J. Pharm. Sci. 2007, 96, 1–26, doi:10.1002/jps.20727.
[17]
Oldham, R.K.; Dillman, R.O. Monoclonal antibodies in cancer therapy: 25 years of progress. J. Clin. Oncol. 2008, 26, 1774–1777, doi:10.1200/JCO.2007.15.7438.
Clynes, R.A.; Towers, T.L.; Presta, L.G.; Ravetch, J.V. Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat. Med. 2000, 6, 443–446, doi:10.1038/74704.
[22]
Graziano, R.F.; Fanger, M.W. Fc gamma RI and Fc gamma RII on monocytes and granulocytes are cytotoxic trigger molecules for tumor cells. J. Immunol. 1987, 139, 3536–3541.
[23]
Kimura, H.; Sakai, K.; Arao, T.; Shimoyama, T.; Tamura, T.; Nishio, K. Antibody-dependent cellular cytotoxicity of cetuximab against tumor cells with wild-type or mutant epidermal growth factor receptor. Cancer Sci. 2007, 98, 1275–1280, doi:10.1111/j.1349-7006.2007.00510.x.
[24]
Jain, R.K. Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy. Nat. Med. 2001, 7, 987–989, doi:10.1038/nm0901-987.
[25]
Chan, A.C.; Carter, P.J. Therapeutic antibodies for autoimmunity and inflammation. Nat. Rev. Immunol. 2010, 10, 301–316, doi:10.1038/nri2761.
[26]
Ducancel, F.; Muller, B.H. Molecular engineering of antibodies for therapeutic and diagnostic purposes. MAbs 2012, 4, 445–457, doi:10.4161/mabs.20776.
[27]
Dillman, R.O. Magic bullets at last! Finally—Approval of a monoclonal antibody for the treatment of cancer!!! Cancer Biother. Radiopharm. 1997, 12, 223–225.
[28]
Huhn, D.; von Schilling, C.; Wilhelm, M.; Ho, A.D.; Hallek, M.; Kuse, R.; Knauf, W.; Riedel, U.; Hinke, A.; Srock, S.; et al. Rituximab therapy of patients with B-cell chronic lymphocytic leukemia. Blood 2001, 98, 1326–1331, doi:10.1182/blood.V98.5.1326.
[29]
Nelson, A.L.; Dhimolea, E.; Reichert, J.M. Development trends for human monoclonal antibody therapeutics. Nat. Rev. Drug Discov. 2010, 9, 767–774, doi:10.1038/nrd3229.
Yamane-Ohnuki, N.; Satoh, M. Production of therapeutic antibodies with controlled fucosylation. MAbs 2009, 1, 230–236, doi:10.4161/mabs.1.3.8328.
[32]
Lis, H.; Sharon, N. Protein glycosylation. Structural and functional aspects. Eur. J. Biochem. 1993, 218, 1–27, doi:10.1111/j.1432-1033.1993.tb18347.x.
[33]
Mimura, Y.; Churcha, S.; Ghirlandob, R.; Ashtonc, S.; Donga, S.; Goodalla, M.; Lunda, J.; Jefferisa, R. The influence of glycosylation on the thermal stability and effector function expression of human IgG1-Fc: Properties of a series of truncated glycoforms. Mol. Immunol. 2000, 37, 697–706, doi:10.1016/S0161-5890(00)00105-X.
[34]
Kayser, V.; Chennamsetty, N.; Voynov, V.; Forrer, K.; Helk, B.; Trout, B.L. Glycosylation influences on the aggregation propensity of therapeutic monoclonal antibodies. Biotechnol. J. 2011, 6, 38–44.
[35]
Runkel, L.; Meier, W.; Blake Pepinsky, R.; Karpusas, M.; Whitty, A.; Kimball, K.; Brickelmaier, M.; Muldowney, C.; Jones, W.; Goelz, S.E. Structural and functional differences between glycosylated and non-glycosylated forms of human interferon-beta (IFN-beta). Pharm. Res. 1998, 15, 641–649, doi:10.1023/A:1011974512425.
[36]
Sondermann, P.; Huber, R.; Oosthuizen, V.; Jacob, U. The 3.2-A crystal structure of the human IgG1 Fc fragment-Fc gammaRIII complex. Nature 2000, 406, 267–273, doi:10.1038/35018508.
Anegon, I.; Cuturi, M.C.; Trinchieri, G.; Perussia, B. Interaction of Fc receptor (CD16) ligands induces transcription of interleukin 2 receptor (CD25) and lymphokine genes and expression of their products in human natural killer cells. J. Exp. Med. 1988, 167, 452–472, doi:10.1084/jem.167.2.452.
[39]
Fanger, M.W.; Graziano, R.F.; Li, S.; Guyre, P.M. Fc gamma R in cytotoxicity exerted by mononuclear cells. Chem. Immunol. 1989, 47, 214–253, doi:10.1159/000318921.
[40]
Anderson, C.L.; Shen, L.; Eicher, D.M.; Wewers, M.D.; Gill, J.K. Phagocytosis mediated by three distinct Fc gamma receptor classes on human leukocytes. J. Exp. Med. 1990, 171, 1333–1345, doi:10.1084/jem.171.4.1333.
[41]
Jefferis, R.; Lund, J.; Pound, J.D. IgG-Fc-mediated effector functions: Molecular definition of interaction sites for effector ligands and the role of glycosylation. Immunol. Rev. 1998, 163, 59–76, doi:10.1111/j.1600-065X.1998.tb01188.x.
[42]
Vugmeyster, Y.; Howell, K. Rituximab-mediated depletion of cynomolgus monkey B cells in vitro in different matrices: Possible inhibitory effect of IgG. Int. Immunopharmacol. 2004, 4, 1117–1124, doi:10.1016/j.intimp.2004.04.015.
[43]
Matsumiya, S.; Yamaguchi, Y.; Saito, J.; Nagano, M.; Sasakawa, H.; Otaki, S.; Satoh, M.; Shitara, K.; Kato, K. Structural comparison of fucosylated and nonfucosylated Fc fragments of human immunoglobulin G1. J. Mol. Biol. 2007, 368, 767–779, doi:10.1016/j.jmb.2007.02.034.
[44]
Ferrara, C.; Stuart, F.; Sondermann, P.; Brünker, P.; Uma？a, P. The carbohydrate at FcgammaRIIIa Asn-162. An element required for high affinity binding to non-fucosylated IgG glycoforms. J. Biol. Chem. 2006, 281, 5032–5036.
[45]
Iida, S.; Misaka, H.; Inoue, M.; Shibata, M.; Nakano, R.; Yamane-Ohnuki, N.; Wakitani, M.; Yano, K.; Shitara, K.; Satoh, M. 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. 2006, 12, 2879–2887, doi:10.1158/1078-0432.CCR-05-2619.
[46]
Shitara, K. Potelligent antibodies as next generation therapeutic antibodies. Yakugaku Zasshi 2009, 129, 3–9, doi:10.1248/yakushi.129.3.
[47]
Wang, W. Instability, stabilization, and formulation of liquid protein pharmaceuticals. Int. J. Pharm. 1999, 185, 29–88, doi:10.1016/S0378-5173(99)00152-0.
[48]
Mahler, H.C.; Friess, W.; Grauschopf, U.; Kiese, S. Protein aggregation: Pathways, induction factors and analysis. J. Pharm. Sci. 2009, 98, 2909–3934, doi:10.1002/jps.21566.
[49]
Daugherty, A.L.; Mrsny, R.J. Formulation and delivery issues for monoclonal antibody therapeutics. Adv. Drug Deliv. Rev. 2006, 58, 686–706, doi:10.1016/j.addr.2006.03.011.
[50]
Parkins, D.A.; Lashmar, U.T. The formulation of biopharmaceutical products. Pharm. Sci. Technol. Today 2000, 3, 129–137, doi:10.1016/S1461-5347(00)00248-0.
[51]
Narhi, L.O.; Jiang, Y.; Cao, S.; Benedek, K.; Shnek, D. A critical review of analytical methods for subvisible and visible particles. Curr. Pharm. Biotechnol. 2009, 10, 373–381, doi:10.2174/138920109788488905.
[52]
Das, T.K. Protein particulate detection issues in biotherapeutics development—Current status. AAPS PharmSciTech. 2012, 13, 732–746, doi:10.1208/s12249-012-9793-4.
[53]
Karshikoff, A. Non-Covalent Interactions in Proteins, 1st ed. ed.; Imperial College Press: London, UK, 2006.
[54]
Andya, J.D.; Hsu, C.C.; Shire, S.J. Mechanisms of aggregate formation and carbohydrate excipient stabilization of lyophilized humanized monoclonal antibody formulations. AAPS PharmSci. 2003, 5, E10, doi:10.1208/ps050209.
[55]
Malencik, D.A.; Anderson, S.R. Dityrosine as a product of oxidative stress and fluorescent probe. Amino Acids 2003, 25, 233–247, doi:10.1007/s00726-003-0014-z.
[56]
Hawe, A.; Kasperb, J.C.; Friessb, W.; Jiskoota, W. Structural properties of monoclonal antibody aggregates induced by freeze-thawing and thermal stress. Eur. J. Pharm. Sci. 2009, 38, 79–87, doi:10.1016/j.ejps.2009.06.001.
[57]
Kreilgaard, L.; Jones, L.S.; Randolph, T.W.; Frokjaer, S.; Flink, J.M.; Manning, M.C.; Carpenter, J.F. Effect of Tween 20 on freeze-thawing- and agitation-induced aggregation of recombinant human factor XIII. J. Pharm. Sci. 1998, 87, 1597–1603.
[58]
Strambini, G.B.; Gonnelli, M. Protein stability in ice. Biophys. J. 2007, 92, 2131–2138, doi:10.1529/biophysj.106.099531.
[59]
Pikal-Cleland, K.A.; Cleland, J.L.; floatdoquy, T.J.; Carpenter, J.F. Effect of glycine on pH changes and protein stability during freeze-thawing in phosphate buffer systems. J. Pharm. Sci. 2002, 91, 1969–1979, doi:10.1002/jps.10184.
[60]
Kueltzo, L.A.; Wang, W.; Randolph, T.W.; Carpenter, J.F. Effects of solution conditions, processing parameters, and container materials on aggregation of a monoclonal antibody during freeze-thawing. J. Pharm. Sci. 2008, 97, 1801–1812, doi:10.1002/jps.21110.
[61]
Schreiber, G. Kinetic studies of protein-protein interactions. Curr. Opin. Struct. Biol. 2002, 12, 41–47, doi:10.1016/S0959-440X(02)00287-7.
[62]
Cleland, J.L.; Powell, M.F.; Shire, S.J. The development of stable protein formulations: A close look at protein aggregation, deamidation, and oxidation. Crit. Rev. Ther. Drug Carrier. Syst. 1993, 10, 307–377.
[63]
Tyler-Cross, R.; Schirch, V. Effects of amino acid sequence, buffers, and ionic strength on the rate and mechanism of deamidation of asparagine residues in small peptides. J. Biol. Chem. 1991, 266, 22549–22556.
[64]
Son, K.; Kwon, C. Stabilization of human epidermal growth factor (hEGF) in aqueous formulation. Pharm. Res. 1995, 12, 451–454, doi:10.1023/A:1016225207014.
[65]
Daniel, R.M.; Dines, M.; Petach, H.H. The denaturation and degradation of stable enzymes at high temperatures. Biochem. J. 1996, 317, 1–11.
[66]
Strickley, R.G.; Anderson, B.D. Solid-state stability of human insulin. I. Mechanism and the effect of water on the kinetics of degradation in lyophiles from pH 2-5 solutions. Pharm. Res. 1996, 13, 1142–1153, doi:10.1023/A:1016043715791.
[67]
Cacia, J.; Keck, R.; Presta, L.G.; Frenz, J. Isomerization of an aspartic acid residue in the complementarity-determining regions of a recombinant antibody to human IgE: Identification and effect on binding affinity. Biochemistry 1996, 35, 1897–1903, doi:10.1021/bi951526c.
[68]
Li, S.; Schoneich, C.; Borchardt, R.T. Chemical pathways of peptide degradation. VIII. Oxidation of methionine in small model peptides by prooxidant/transition metal ion systems: Influence of selective scavengers for reactive oxygen intermediates. Pharm. Res. 1995, 12, 348–355, doi:10.1023/A:1016240115675.
[69]
Powell, M.F. A compendium and hydropathy/flexibility analysis of common reactive sites in proteins: Reactivity at Asn, Asp, Gln, and Met motifs in neutral pH solution. In Formulation, Characterization, and Stability of Protein Drugs; Pearlman, R., Wang, Y.J., Eds.; Plenum Press: New York, NY, USA, 1996; pp. 1–140.
[70]
Brange, J.; Langkj, L.; Havelund, S.; V？lund, A. Chemical stability of insulin. 1. Hydrolytic degradation during storage of pharmaceutical preparations. Pharm. Res. 1992, 9, 715–726, doi:10.1023/A:1015835017916.
[71]
Manning, M.C.; Patel, K.; Borchardt, R.T. Stability of protein pharmaceuticals. Pharm. Res. 1989, 6, 903–918, doi:10.1023/A:1015929109894.
[72]
Kroon, D.J.; Baldwin-Ferro, A.; Lalan, P. Identification of sites of degradation in a therapeutic monoclonal antibody by peptide mapping. Pharm. Res. 1992, 9, 1386–1393, doi:10.1023/A:1015894409623.
[73]
Li, S.; Nguyen, T.H.; Schoneich, C.; Borchardt, R.T. Aggregation and precipitation of human relaxin induced by metal-catalyzed oxidation. Biochemistry 1995, 34, 5762–5772, doi:10.1021/bi00017a008.
[74]
Lam, X.M.; Yang, J.Y.; Cleland, J.L. Antioxidants for prevention of methionine oxidation in recombinant monoclonal antibody HER2. J. Pharm. Sci. 1997, 86, 1250–1255, doi:10.1021/js970143s.
[75]
Ha, E.; Wang, W.; Wang, Y.J. Peroxide formation in polysorbate 80 and protein stability. J. Pharm. Sci. 2002, 91, 2252–2264, doi:10.1002/jps.10216.
[76]
Knepp, V.M.; Whatley, J.L.; Muchnik, A.; Calderwood, T.S. Identification of antioxidants for prevention of peroxide-mediated oxidation of recombinant human ciliary neurotrophic factor and recombinant human nerve growth factor. PDA J. Pharm. Sci. Technol. 1996, 50, 163–171.
[77]
Liu, J.L.; Lu, K.V.; Eris, T.; Katta, V.; Westcott, K.R.; Narhi, L.O.; Lu, H.S. In vitro methionine oxidation of recombinant human leptin. Pharm. Res. 1998, 15, 632–640, doi:10.1023/A:1011998331254.
[78]
Fransson, J.; FIorin-Robertsson, E.; Axelsson, K.; Nyhlén, C. Oxidation of human insulin-like growth factor I in formulation studies: Kinetics of methionine oxidation in aqueous solution and in solid state. Pharm. Res. 1996, 13, 1252–1257, doi:10.1023/A:1016032808039.
[79]
Shahrokh, Z.; Eberlein, G.; Buckley, D.; Paranandi, M.V.; Aswad, D.W.; Stratton, P.; Mischak, R.; Wang, Y.J. Major degradation products of basic fibroblast growth factor: Detection of succinimide and iso-aspartate in place of aspartate. Pharm. Res. 1994, 11, 936–944, doi:10.1023/A:1018962732067.
[80]
Kamat, M.S.; Tolman, G.L.; Brown, J.M. Formulation development of an antifibrin monoclonal antibody radiopharmaceutical. Pharm. Biotechnol. 1996, 9, 343–364, doi:10.1007/0-306-47452-2_9.
[81]
Tous, G.I.; Wei, Z.; Feng, J.; Bilbulian, S.; Bowen, S.; Smith, J.; Strouse, R.; McGeehan, P.; Casas-Finet, J.; Schenerman, M.A. Characterization of a novel modification to monoclonal antibodies: Thioether cross-link of heavy and light chains. Anal. Chem. 2005, 77, 2675–2682, doi:10.1021/ac0500582.
[82]
Hermeling, S.; Crommelin, D.J.A.; Schellekens, H.; Jiskoot, W. Structure-immunogenicity relationships of therapeutic proteins. Pharm. Res. 2004, 21, 897–903, doi:10.1023/B:PHAM.0000029275.41323.a6.
[83]
Schellekens, H. Immunogenicity of therapeutic proteins: Clinical implications and future prospects. Clin. Ther. 2002, 24, 1720–1740; discussion 1719, doi:10.1016/S0149-2918(02)80075-3.
[84]
Casadevall, N.; Nataf, J.; Viron, B.; Kolta, A.; Kiladjian, J.-J.; Martin-Dupont, P.; Michaud, P.; Papo, T.; Ugo, V.; Teyssandier, I.; et al. Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N. Engl. J. Med. 2002, 346, 469–475, doi:10.1056/NEJMoa011931.
[85]
Joubert, M.K.; Hokom, M.; Eakin, C.; Zhou, L.; Deshpande, M.; Baker, M.P.; Goletz, T.J.; Kerwin, B.A.; Chirmule, N.; Narhi, L.O.; et al. Highly aggregated antibody therapeutics can enhance the in vitro innate and late-stage T-cell immune responses. J. Biol. Chem. 2012, 287, 25266–25279, doi:10.1074/jbc.M111.330902.
[86]
Demeule, B.; Gurny, R.; Arvinte, T. Where disease pathogenesis meets protein formulation: Renal deposition of immunoglobulin aggregates. Eur. J. Pharm. Biopharm. 2006, 62, 121–130, doi:10.1016/j.ejpb.2005.08.008.
[87]
USP. General Chapters: <788> Particulate Matter in Injections; Pharmacopeial Forum: Maryland, MD, USA, 2009; pp. SP32–NF27.
[88]
Harris, R.J.; Kabakoff, B.; Macchi, F.D.; Shen, F.J.; Kwong, M.; Andya, J.D.; Shire, S.J.; Bjork, N.; Totpal, K.; Chen, A.B. Identification of multiple sources of charge heterogeneity in a recombinant antibody. J. Chromatogr. B Biomed. Sci. Appl. 2001, 752, 233–245, doi:10.1016/S0378-4347(00)00548-X.
[89]
Hochuli, E. Interferon immunogenicity: Technical evaluation of interferon-alpha 2a. J. Interferon. Cytokine Res. 1997, 17, S15–S21.
[90]
Laue, T.M.; Shah, B.; Ridgeway, T.M.; Pelletier, S.L. Computer-aided Interpretation of Sedimentation Data for Proteins. In Analytical Ultracentrifugation in Biochemistry and Polymer Science; Harding, S.E., Rowe, A.J., Horton, J.C., Eds.; Royal Society of Chemistry: Cambridge, UK, 1992; pp. 90–125.
[91]
Hartmann, W.K.; Saptharishi, N.; Yang, X.Y.; Mitra, G.; Soman, G. Characterization and analysis of thermal denaturation of antibodies by size exclusion high-performance liquid chromatography with quadruple detection. Anal. Biochem. 2004, 325, 227–239, doi:10.1016/j.ab.2003.10.031.
[92]
Chiti, F.; van Nuland, N.A.J.; Taddei, N.; Magherini, F.; Stefani, M.; Ramponi, G.; Dobson, C.M. Conformational stability of muscle acylphosphatase: The role of temperature, denaturant concentration, and pH. Biochemistry 1998, 37, 1447–1455, doi:10.1021/bi971692f.
[93]
PharmaCircle. Available online: www.pharmacircle.com (accessed on 1 June 2013).
[94]
Lam, X.M.; Oeswein, O.J.; Ongpipattanakul, B.; Shahrokh, Z.; Weissburg, W.S.; Wong, R.P. Stabilized Antibody Formulation. US Patent CA 2292730, 1998.
[95]
Johnson, R.E.; Hong, Q.I.; Borgmeyer, J.R.; Kessler, R.K.; Zeng, D.L. Stable pH optimized formulation of a modified antibody. WO Patent WO/2004/019861, 2004.
[96]
Warne, N.W. Development of high concentration protein biopharmaceuticals: The use of platform approaches in formulation development. Eur. J. Pharm. Biopharm. 2011, 78, 208–212, doi:10.1016/j.ejpb.2011.03.004.
[97]
Lee, L.S. Stabilized Monomeric Protein Compositions. US Patent 5,656,730, 1997.
[98]
Worn, A.; Pluckthun, A. Mutual stabilization of VL and VH in single-chain antibody fragments, investigated with mutants engineered for stability. Biochemistry 1998, 37, 13120–13127, doi:10.1021/bi980712q.
[99]
Horbett, T.A. Protein adsorption on biomaterials. In Biomaterials: Interfacial Phenomena and Applications; Cooper, S.L., Peppas, N.A., Hoffman, A.S., Ratner, B.D., Eds.; American Chemical Society: Washington DC, USA, 1982; pp. 233–244.
[100]
Lee, H.J.; McAuley, A.; Schilke, K.F.; McGuire, J. Molecular origins of surfactant-mediated stabilization of protein drugs. Adv. Drug Deliv. Rev. 2011, 63, 1160–1171, doi:10.1016/j.addr.2011.06.015.
[101]
Kerwin, B.A. Polysorbates 20 and 80 used in the formulation of protein biotherapeutics: Structure and degradation pathways. J. Pharm. Sci. 2008, 97, 2924–2935, doi:10.1002/jps.21190.
[102]
Chen, B.; Bautista, R.; Yu, K.; Zapata, G.A.; Mulkerrin, M.G.; Chamow, S.M. Influence of histidine on the stability and physical properties of a fully human antibody in aqueous and solid forms. Pharm. Res. 2003, 20, 1952–1960, doi:10.1023/B:PHAM.0000008042.15988.c0.
[103]
Paborji, M.; Pochopin, N.L.; Coppola, W.P.; Bogardus, J.B. Chemical and physical stability of chimeric L6, a mouse-human monoclonal antibody. Pharm. Res. 1994, 11, 764–771, doi:10.1023/A:1018948901599.
[104]
McIntosh, K.A.; Charman, W.N.; Charman, S.A. The application of capillary electrophoresis for monitoring effects of excipients on protein conformation. J. Pharm. Biomed. Anal. 1998, 16, 1097–1105, doi:10.1016/S0731-7085(97)00096-4.
[105]
Li, S.; Patapoff, T.W.; Nguyen, T.H.; Borchardt, R.T. Inhibitory effect of sugars and polyols on the metal-catalyzed oxidation of human relaxin. J. Pharm. Sci. 1996, 85, 868–872, doi:10.1021/js9504550.
[106]
Li, S.; Patapoff, T.W.; Overcashier, D.; Hsu, C.; Nguyen, T.H.; Borchardt, R.T. Effects of reducing sugars on the chemical stability of human relaxin in the lyophilized state. J. Pharm. Sci. 1996, 85, 873–877, doi:10.1021/js950456s.
[107]
Ji, J.A.; Zhang, B.; Cheng, W.; John Wang, Y. Methionine, tryptophan, and histidine oxidation in a model protein, PTH: Mechanisms and stabilization. J. Pharm. Sci. 2009, 98, 4485–4500, doi:10.1002/jps.21746.
[108]
Gokarn, Y.R.; Matthew Fesinmeyer, R.; Saluja, A.; Razinkov, V.; Chase, S.F.; Laue, T.M.; Brems, D.N. Effective charge measurements reveal selective and preferential accumulation of anions, but not cations, at the protein surface in dilute salt solutions. Protein Sci. 2011, 20, 580–587, doi:10.1002/pro.591.
[109]
Fesinmeyer, R.M.; Hogan, S.; Saluja, A.; Brych, S.R.; Kras, E.; Narhi, L.O.; Brems, D.N.; Gokarn, Y.R. Effect of ions on agitation- and temperature-induced aggregation reactions of antibodies. Pharm. Res. 2009, 26, 903–913, doi:10.1007/s11095-008-9792-z.
[110]
Laue, T. Proximity energies: A framework for understanding concentrated solutions. J. Mol. Recognit. 2012, 25, 165–173, doi:10.1002/jmr.2179.
[111]
Adams, G.P.; Schier, R.; McCall, A.M.; Crawford, R.S.; Wolf, E.J.; Weiner, L.M.; Marks, J.D. Prolonged in vivo tumour retention of a human diabody targeting the extracellular domain of human HER2/neu. Br. J. Cancer 1998, 77, 1405–1412, doi:10.1038/bjc.1998.233.
[112]
Di Fede, G.; Bronte, G.; Rizzo, S.; Cervetto, C.R.; Cocorullo, G.; Gulotta, G.; Bazan, V.; Russo, A. Monoclonal antibodies and antibody fragments: State of the art and future perspectives in the treatment of non-haematological tumors. Expert Opin. Biol. Ther. 2011, 11, 1433–1445, doi:10.1517/14712598.2011.594436.
[113]
Stockwin, L.H.; Holmes, S. Antibodies as therapeutic agents: Vive la renaissance! Expert Opin. Biol. Ther. 2003, 3, 1133–1152, doi:10.1517/14712598.3.7.1133.
[114]
Bookbinder, L.H.; Hofera, A.; Hallera, M.F.; Zepedab, M.L.; Kellera, G.-A.; Lima, J.E.; Edgingtonc, T.S.; Shepardd, H.M.; Pattone, J.S.; Frosta, G.I. A recombinant human enzyme for enhanced interstitial transport of therapeutics. J. Control Release 2006, 114, 230–241, doi:10.1016/j.jconrel.2006.05.027.
[115]
Gatlin, L.A.; Gatlin, C.A.B. Formulation and administration techniques to minimize injection pain and tissue damage associated with parenteral products. In Injectable Drug Development: Techniques to Reduce Pain and Irritation; Gapta, P.K., Brazeau, G.A., Eds.; Interpharm Press: Denver, CO, USA, 1999; pp. 401–425.
[116]
Yu, A.W.; Leung, C.B.; Li, P.K.; Lui, S.F.; Lai, K.N. Pain perception following subcutaneous injections of citrate-buffered and phosphate-buffered epoetin alpha. Int. J. Artif. Organs. 1998, 21, 41–43.
Laursen, T.; Hansen, B.; Fisker, S. Pain perception after subcutaneous injections of media containing different buffers. Basic Clin. Pharmacol. Toxicol. 2006, 98, 218–221, doi:10.1111/j.1742-7843.2006.pto_271.x.
Rivas, G.; Minton, A.P. Non-ideal tracer sedimentation equilibrium: A powerful tool for the characterization of macromolecular interactions in crowded solutions. J. Mol. Recognit. 2004, 17, 362–367, doi:10.1002/jmr.708.
[121]
Yadav, S.; Laue, T.M.; Kalonia, D.S.; Singh, S.N.; Shire, S.J. The influence of charge distribution on self-association and viscosity behavior of monoclonal antibody solutions. Mol. Pharm. 2012, 9, 791–802.
[122]
Schein, C.H. Solubility as a function of protein structure and solvent components. Biotechnology 1990, 8, 308–317.
[123]
Shire, S.J.; Shahrokh, Z.; Liu, J. Challenges in the development of high protein concentration formulations. J. Pharm. Sci. 2004, 93, 1390–1402, doi:10.1002/jps.20079.
[124]
Sukumar, M.; Doyle, B.L.; Combs, J.L.; Pekar, A.H. Opalescent appearance of an IgG1 antibody at high concentrations and its relationship to noncovalent association. Pharm. Res. 2004, 21, 1087–1093, doi:10.1023/B:PHAM.0000032993.98705.73.
[125]
Cromwell, M.E.M.; Carpenter, J.F.; Scherer, T.; Randolph, T.J. Opalescence in Antibody Formulations is a Solution Critical Phenomenon. In Proceseedings of the 236th ACS National Meeting, Philadelphia, PA, USA, 2008.
[126]
Saluja, A.; Kalonia, D.S. Nature and consequences of protein-protein interactions in high protein concentration solutions. Int. J. Pharm. 2008, 358, 1–15, doi:10.1016/j.ijpharm.2008.03.041.
Shire, S.J.; Liu, J.; Friess, W.; J？rg, S.; Mahler, H.-C. High-concentration antibody formulations. In Formulation and Process Development Strategies for Manufacturing Biopharmaceuticals; Hershenson, F.J.S., Ed.; John Wiley & Sons, Inc: Hoboken, NJ, USA, 2010.
[130]
Friess, H.; Langrehr, J.M.; Oettle, H.; Raedle, J.; Niedergethmann, M.; Dittrich, C.; Hossfeld, D.K.; St？ger, H.; Neyns, B.; Herzog, P.; et al. A randomized multi-center phase II trial of the angiogenesis inhibitor Cilengitide (EMD 121974) and gemcitabine compared with gemcitabine alone in advanced unresectable pancreatic cancer. BMC Cancer 2006, 6, 285, doi:10.1186/1471-2407-6-285.
[131]
Rathore, N.; Pranay, P.; Bernacki, J.; Eu, B.; Ji, W.; Walls, E. Characterization of protein rheology and delivery forces for combination products. J. Pharm. Sci. 2012, 101, 4472–4480, doi:10.1002/jps.23297.
[132]
Harris, R.J.; Shire, S.J.; Winter, C. Commercial manufacturing scale formulation and analytical characterization of therapeutic recombinant antibodies. Drug Develop. Res. 2004, 61, 137–154, doi:10.1002/ddr.10344.
[133]
Jimenez, M.; Rivas, G.; Minton, A.P. Quantitative characterization of weak self-association in concentrated solutions of immunoglobulin G via the measurement of sedimentation equilibrium and osmotic pressure. Biochemistry 2007, 46, 8373–8378, doi:10.1021/bi7005515.
Kroe, R.R.; Laue, T.M. NUTS and BOLTS: Applications of fluorescence-detected sedimentation. Anal. Biochem. 2009, 390, 1–13, doi:10.1016/j.ab.2008.11.033.
[136]
MacGregor, I.K.; Anderson, A.L.; Laue, T.M. Fluorescence detection for the XLI analytical ultracentrifuge. Biophys. Chem. 2004, 108, 165–185, doi:10.1016/j.bpc.2003.10.018.
[137]
Scherer, T.; Kanai, S.; Liu, J.; Shire, S. Characterization of monoclonal antibodies at high concentrations by light scattering. In Proceedings of AAPS National Biotechnology Conference, San Diego, CA, USA, 2007.
[138]
Ross, P.D.; Minton, A.P. Analysis of non-ideal behavior in concentrated hemoglobin solutions. J. Mol. Biol. 1977, 112, 437–452, doi:10.1016/S0022-2836(77)80191-5.
[139]
Yousef, M.A.; Datta, R.; Rodgers, V.G.J. Free-Solvent Model of Osmotic Pressure Revisited: Application to Concentrated IgG Solution under Physiological Conditions. J. Colloid. Interface Sci. 1998, 197, 108–118, doi:10.1006/jcis.1997.5262.
[140]
Paliwal, A.; Asthagiri, D.; Abras, D.; Lenhoff, A.M.; Paulaitis, M.E. Light-scattering studies of protein solutions: Role of hydration in weak protein-protein interactions. Biophys. J. 2005, 89, 1564–1573, doi:10.1529/biophysj.105.065284.
[141]
Neal, B.L.; Asthagiri, D.; Lenhoff, A.M. Molecular origins of osmotic second virial coefficients of proteins. Biophys. J. 1998, 75, 2469–2477, doi:10.1016/S0006-3495(98)77691-X.
[142]
Salinas, B.A.; Sathish, H.A.; Bishop, S.M.; Harn, N.; Carpenter, J.F.; Randolph, T.W. Understanding and modulating opalescence and viscosity in a monoclonal antibody formulation. J. Pharm. Sci. 2010, 99, 82–93, doi:10.1002/jps.21797.
[143]
Saito, S.; Hasegawa, J.; Kobayashi, N.; Kishi, N.; Uchiyama, S.; Fukui, K. Behavior of monoclonal antibodies: Relation between the second virial coefficient (B (2)) at low concentrations and aggregation propensity and viscosity at high concentrations. Pharm. Res. 2012, 29, 397–410, doi:10.1007/s11095-011-0563-x.
[144]
Attri, A.K.; Minton, A.P. New methods for measuring macromolecular interactions in solution via static light scattering: Basic methodology and application to nonassociating and self-associating proteins. Anal. Biochem. 2005, 337, 103–110, doi:10.1016/j.ab.2004.09.045.
[145]
Alford, J.R.; Kendrick, B.S.; Carpenter, J.F.; Randolph, T.W. Measurement of the second osmotic virial coefficient for protein solutions exhibiting monomer-dimer equilibrium. Anal. Biochem. 2008, 377, 128–133, doi:10.1016/j.ab.2008.03.032.
[146]
Some, D.; Kenrick, S. Characterization of protein-protein interactions via static and dynamic light scattering, in rotein interaction. In Protein Interactions; Cai, J., Ed.; InTech.: Rijeka, Croatia, 2012.
[147]
Le Brun, V.; Friess, W.; Bassarab, S.; Garidel, P. Correlation of protein-protein interactions as assessed by affinity chromatography with colloidal protein stability: A case study with lysozyme. Pharm. Dev. Technol. 2010, 15, 421–430, doi:10.3109/10837450903262074.
[148]
Le Brun, V.; Friess, W.; Bassarab, S.; Mühlau, S.; Garidel, P. A critical evaluation of self-interaction chromatography as a predictive tool for the assessment of protein-protein interactions in protein formulation development: A case study of a therapeutic monoclonal antibody. Eur. J. Pharm. Biopharm. 2010, 75, 16–25, doi:10.1016/j.ejpb.2010.01.009.
[149]
Deszczynski, M.; Harding, S.E.; Winzor, D.J. Negative second virial coefficients as predictors of protein crystal growth: Evidence from sedimentation equilibrium studies that refutes the designation of those light scattering parameters as osmotic virial coefficients. Biophys. Chem. 2006, 120, 106–113, doi:10.1016/j.bpc.2005.10.003.
[150]
Tessier, P.M.; Lenhoff, A.M.; Sandler, S.I. Rapid measurement of protein osmotic second virial coefficients by self-interaction chromatography. Biophys. J. 2002, 82, 1620–1631, doi:10.1016/S0006-3495(02)75513-6.
[151]
Saluja, A.; Matthew Fesinmeyer, R.; Hogan, S.; Brems, D.N. Diffusion and sedimentation interaction parameters for measuring the second virial coefficient and their utility as predictors of protein aggregation. Biophys. J. 2010, 99, 2657–2665, doi:10.1016/j.bpj.2010.08.020.
[152]
Harding, S.E.; Johnson, P. The concentration-dependence of macromolecular parameters. Biochem. J. 1985, 231, 543–547.
[153]
Connolly, B.D.; Petry, C.; Yadav, S.; Demeule, B.; Ciaccio, N.; Moore, J.M.R.; Shire, S.J.; Gokarn, Y.R. Weak interactions govern the viscosity of concentrated antibody solutions: High-throughput analysis using the diffusion interaction parameter. Biophys. J. 2012, 103, 69–78, doi:10.1016/j.bpj.2012.04.047.
[154]
Winzor, D.J.; Jones, S.; Harding, S.E. Determination of protein charge by capillary zone electrophoresis. Anal. Biochem. 2004, 333, 225–229, doi:10.1016/j.ab.2004.05.013.
[155]
Durant, J.A.; Chen, C.; Laue, T.M.; Moody, T.P.; Allison, S.A. Use of T4 lysozyme charge mutants to examine electrophoretic models. Biophys. Chem. 2002, 101–102, 593–609, doi:10.1016/S0301-4622(02)00168-0.
[156]
WYATT. Available online: www.wyatt.com (accessed on 1 June 2013).
[157]
Minton, A.P. Molecular crowding: Analysis of effects of high concentrations of inert cosolutes on biochemical equilibria and rates in terms of volume exclusion. Methods Enzymol. 1998, 295, 127–149, doi:10.1016/S0076-6879(98)95038-8.
[158]
Janthur, W.-D.; Cantoni, N.; Mamot, C. Drug Conjugates Such as Antibody Drug Conjugates (ADCs), Immunotoxins and Immunoliposomes Challenge Daily Clinical Practice. Int. J. Mol. Sci. 2012, 13, 16020–16045, doi:10.3390/ijms131216020.
Lam, K.C.L.; Rajaraman, G. Assessment of P-glycoprotein substrate and inhibition potential of test compounds in MDR1-transfected MDCK cells. Curr. Protoc. Pharmacol. 2012, doi:10.1002/0471141755.ph0713s58.
[164]
Krech, T.; Scheuerera, E.; Geffers, R.; Kreipe, H.; Lehmann, U.; Christgen, M. ABCB1/MDR1 contributes to the anticancer drug-resistant phenotype of IPH-926 human lobular breast cancer cells. Cancer Lett. 2012, 315, 153–160, doi:10.1016/j.canlet.2011.09.038.
[165]
Bidwell, G.L., 3rd; Davis, A.N.; Fokt, I.; Priebe, W.; Raucher, D. A thermally targeted elastin-like polypeptide-doxorubicin conjugate overcomes drug resistance. Invest. New Drugs 2007, 25, 313–326, doi:10.1007/s10637-007-9053-8.
[166]
Hughes, B. Antibody-drug conjugates for cancer: Poised to deliver? Nat. Rev. Drug Discov. 2010, 9, 665–667, doi:10.1038/nrd3270.
[167]
Barginear, M.F.; John, V.; Budman, D.R. Trastuzumab-DM1: A clinical update of the novel antibody-drug conjugate for HER2-overexpressing breast cancer. Mol. Med. 2013, 18, 1473–1479.
[168]
Rowland, G.F.; O'Neill, G.J.; Davies, D.A. Suppression of tumour growth in mice by a drug-antibody conjugate using a novel approach to linkage. Nature 1975, 255, 487–488, doi:10.1038/255487a0.
[169]
Beck, A.; Lambert, J.; Sun, M.; Lin, K. Fourth World Antibody-Drug Conjugate Summit: February 29-March 1, 2012, Frankfurt, Germany. MAbs 2012, 4, 637–647, doi:10.4161/mabs.21697.
[170]
Xie, H.; Audette, C.; Hoffee, M.; Lambert, J.M.; Bl？ttler, W.A. Pharmacokinetics and biodistribution of the antitumor immunoconjugate, cantuzumab mertansine (huC242-DM1), and its two components in mice. J. Pharmacol. Exp. Ther. 2004, 308, 1073–1082.
[171]
Ducry, L.; Stump, B. Antibody-drug conjugates: Linking cytotoxic payloads to monoclonal antibodies. Bioconjug. Chem. 2010, 21, 5–13, doi:10.1021/bc9002019.
[172]
Dosio, F.; Brusa, P.; Cattel, L. Immunotoxins and anticancer drug conjugate assemblies: The role of the linkage between components. Toxins (Basel) 2011, 3, 848–883, doi:10.3390/toxins3070848.
[173]
Hamblett, K.J.; Senter, P.D.; Chace, D.F.; Sun, M.M.C.; Lenox, J.; Cerveny, C.G.; Kissler, K.M.; Bernhardt, S.X.; Kopcha, A.K.; Zabinski, R.F. Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate. Clin. Cancer Res. 2004, 10, 7063–7070, doi:10.1158/1078-0432.CCR-04-0789.
[174]
Le, L.N.; Moore, J.M.R.; Ouyang, J.; Chen, X.; Nguyen, M.D.H.; Galush, W.J. Profiling antibody drug conjugate positional isomers: A system-of-equations approach. Anal. Chem. 2012, 84, 7479–7486, doi:10.1021/ac301568f.
[175]
Liu, H.; Chumsae, C.; Gaza-Bulseco, G.; Hurkmans, K.; Radziejewski, C.H. Ranking the susceptibility of disulfide bonds in human IgG1 antibodies by reduction, differential alkylation, and LC-MS analysis. Anal. Chem. 2010, 82, 5219–5226, doi:10.1021/ac100575n.
[176]
Sun, M.M.; Beam, K.S.; Cerveny, C.G.; Hamblett, K.J.; Blackmore, R.S.; Torgov, M.Y.; Handley, F.G.M.; Ihle, N.C.; Senter, P.D.; Alley, S.C. Reduction-alkylation strategies for the modification of specific monoclonal antibody disulfides. Bioconjug. Chem. 2005, 16, 1282–1290, doi:10.1021/bc050201y.
[177]
Dornan, D.; Bennett, F.; Chen, Y.; Dennis, M.; Eaton, D.; Elkins, K.; French, D.; Go, M.A.T.; Jack, A.; Junutula, J.R.; et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood 2009, 114, 2721–2729, doi:10.1182/blood-2009-02-205500.
[178]
Junutula, J.R.; Raab, H.; Clark, S.; Bhakta, S.; Leipold, D.D.; Weir, S.; Chen, Y.; Simpson, M.; Tsai, S.P.; Dennis, M.S.; et al. Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat. Biotechnol. 2008, 26, 925–932, doi:10.1038/nbt.1480.
[179]
Shen, B.Q.; Xu, K.; Liu, L.; Raab, H.; Bhakta, S.; Kenrick, M.; Parsons-Reponte, K.L.; Tien, J.; Yu, S.-F.; Mai, E.; et al. Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates. Nat. Biotechnol. 2012, 30, 184–189, doi:10.1038/nbt.2108.
[180]
Axup, J.Y.; Bajjuri, K.M.; Ritland, M.; Hutchinsa, B.M.; Kima, C.H.; Kazane, S.A. ; Halder, R.; Forsyth, J.S.; Santidrian, A.F.; Stafin, K.; et al. Synthesis of site-specific antibody-drug conjugates using unnatural amino acids. Proc. Natl. Acad. Sci. USA 2012, 109, 16101–16106.
[181]
Presentini, R.; Terrana, B. Influence of the antibody-peroxidase coupling methods on the conjugate stability and on the methodologies for the preservation of the activity in time. J. Immunoassay 1995, 16, 309–324, doi:10.1080/15321819508013565.
[182]
Fishkin, N.; Maloney, E.K.; Chari, R.V.J.; Singh, R. A novel pathway for maytansinoid release from thioether linked antibody-drug conjugates (ADCs) under oxidative conditions. Chem. Commun. (Camb) 2011, 47, 10752–10754.
[183]
Ryan, C.P.; Smith, M.E.B.; Schumacher, F.F.; Grohmann, D.; Papaioannou, D.; Waksman, G.; Werner, F.; Baker, J.R.; Caddick, S. Tunable reagents for multi-functional bioconjugation: Reversible or permanent chemical modification of proteins and peptides by control of maleimide hydrolysis. Chem. Commun. (Camb) 2011, 47, 5452–5454, doi:10.1039/c1cc11114k.
[184]
Doronina, S.O.; Mendelsohn, B.A.; Bovee, T.D.; Cerveny, C.G.; Alley, S.C.; Meyer, D.L.; Oflazoglu, E.; Toki, B.E.; Sanderson, R.J.; Zabinski, R.F.; et al. Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: Effects of linker technology on efficacy and toxicity. Bioconjug. Chem. 2006, 17, 114–124, doi:10.1021/bc0502917.
Sapra, P.; Damelin, M.; DiJoseph, J.; Marquette, K.; Geles, K.G.; Golas, J.; Dougher, M.; Narayanan, B.; Giannakou, A.; Khandke, K.; et al. Long-term tumor regression induced by an antibody-drug conjugate that targets 5T4, an oncofetal antigen expressed on tumor-initiating cells. Mol. Cancer Ther. 2013, 12, 38–47.
[187]
Polson, A.G.; Calemine-Fenaux, J.; Chan, P.; Chang, W.; Christensen, E.; Clark, S.; de Sauvage, F.J.; Eaton, D.; Elkins, K.; Michael Elliott, J.; et al. Antibody-drug conjugates for the treatment of non-Hodgkin's lymphoma: Target and linker-drug selection. Cancer Res. 2009, 69, 2358–2364, doi:10.1158/0008-5472.CAN-08-2250.
[188]
Erickson, H.K.; Park, P.U.; Widdison, W.C.; Kovtun, Y.V.; Garrett, L.M.; Hoffman, K.; Lutz, R.J.; Goldmacher, V.S.; Bl？ttler, W.A. Antibody-maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res. 2006, 66, 4426–4433, doi:10.1158/0008-5472.CAN-05-4489.
[189]
Oflazoglu, E.; Stone, I.J.; Gordon, K.; Wood, C.G.; Repasky, E.A.; Grewal, I.S.; Law, C.-L.; Gerber, H.-P. Potent anticarcinoma activity of the humanized anti-CD70 antibody h1F6 conjugated to the tubulin inhibitor auristatin via an uncleavable linker. Clin. Cancer Res. 2008, 14, 6171–6180, doi:10.1158/1078-0432.CCR-08-0916.
[190]
Hollander, I.; Kunz, A.; Hamann, P.R. Selection of reaction additives used in the preparation of monomeric antibody-calicheamicin conjugates. Bioconjug. Chem. 2008, 19, 358–361, doi:10.1021/bc700321z.
[191]
Wakankar, A.A.; Feeney, M.B.; Rivera, J.; Chen, Y.; Kim, M.; Sharma, V.K.; John Wang, Y. Physicochemical stability of the antibody-drug conjugate Trastuzumab-DM1: Changes due to modification and conjugation processes. Bioconjug. Chem. 2010, 21, 1588–1595, doi:10.1021/bc900434c.
[192]
Quiles, S.; Raisch, K.P.; Sanford, L.L.; Bonner, J.A.; Safavy, A. Synthesis and preliminary biological evaluation of high-drug-load paclitaxel-antibody conjugates for tumor-targeted chemotherapy. J. Med. Chem. 2010, 53, 586–594, doi:10.1021/jm900899g.
[193]
King, H.D.; Yurgaitis, D.; Willner, D.; Firestone, R.A.; Yang, M.B.; Lasch, S.J.; Hellstr？m, K.E.; Trail, P.A. Monoclonal antibody conjugates of doxorubicin prepared with branched peptide linkers: Inhibition of aggregation by methoxytriethyleneglycol chains. J. Med. Chem. 2002, 45, 4336–4343, doi:10.1021/jm020149g.
[194]
Kafi, K.; Betting, D.J.; Yamada, R.E.; Bacica, M.; Steward, K.K.; Timmerman, J.M. Maleimide conjugation markedly enhances the immunogenicity of both human and murine idiotype-KLH vaccines. Mol. Immunol. 2009, 46, 448–456, doi:10.1016/j.molimm.2008.10.020.
[195]
Christie, R.J.; Anderson, D.J.; Grainger, D.W. Comparison of hydrazone heterobifunctional cross-linking agents for reversible conjugation of thiol-containing chemistry. Bioconjug. Chem. 2010, 21, 1779–1787, doi:10.1021/bc100049c.
[196]
Bagshawe, K.D. Targeting: The ADEPT story so far. Curr. Drug Targets 2009, 10, 152–157, doi:10.2174/138945009787354520.
Vogelzang, N.J.; Porta, C.; Mutti, L. New agents in the management of advanced mesothelioma. Semin. Oncol. 2005, 32, 336–350, doi:10.1053/j.seminoncol.2005.02.010.
[199]
Pavlakis, N.; Vogelzang, N.J. Ranpirnase—An antitumour ribonuclease: Its potential role in malignant mesothelioma. Expert Opin. Biol. Ther. 2006, 6, 391–399, doi:10.1517/14712598.6.4.391.
[200]
Rosenblum, M.G.; Barth, S. Development of novel, highly cytotoxic fusion constructs containing granzyme B: Unique mechanisms and functions. Curr. Pharm. Des. 2009, 15, 2676–2692, doi:10.2174/138161209788923958.
[201]
Kurschus, F.C.; Kleinschmidt, M.; Fellows, E.; Dornmair, K.; Rudolph, R.; Lilie, H.; Jenne, D.E. Killing of target cells by redirected granzyme B in the absence of perforin. FEBS Lett. 2004, 562, 87–92, doi:10.1016/S0014-5793(04)00187-5.
[202]
Weidle, U.H.; Georges, G.; Brinkmann, U. Fully human targeted cytotoxic fusion proteins: New anticancer agents on the horizon. Cancer Genomics Proteomics 2012, 9, 119–133.
[203]
Larrick, J.W.; Cresswell, P. Modulation of cell surface iron transferrin receptors by cellular density and state of activation. J. Supramol. Struct. 1979, 11, 579–586, doi:10.1002/jss.400110415.
[204]
Kordower, J.H.; Charles, V.; Bayer, R.; Bartus, R.T.; Putney, S.; Walus, L.R.; Friden, P.M. Intravenous administration of a transferrin receptor antibody-nerve growth factor conjugate prevents the degeneration of cholinergic striatal neurons in a model of Huntington disease. Proc. Natl. Acad. Sci. USA 1994, 91, 9077–9080, doi:10.1073/pnas.91.19.9077.
[205]
Granholm, A.C.; Albeck, D.; B？ckman, C.; Curtis, M.; Ebendal, T.; Friden, P.; Henry, M.; Hoffer, B.; Kordower, J.; Rose, G.M.; et al. A non-invasive system for delivering neural growth factors across the blood-brain barrier: A review. Rev. Neurosci. 1998, 9, 31–55.
[206]
McGrath, J.P.; Cao, X.; Schutz, A.; Lynch, P.; Ebendal, T.; Josephina Coloma, M.; Morrison, S.L.; Putney, S.D. Bifunctional fusion between nerve growth factor and a transferrin receptor antibody. J. Neurosci. Res. 1997, 47, 123–133, doi:10.1002/(SICI)1097-4547(19970115)47:2<123::AID-JNR1>3.0.CO;2-H.
[207]
Penichet, M.L.; Kang, Y.-S.; Pardridge, W.M.; Morrison, S.L.; Shin, S.-U. An antibody-avidin fusion protein specific for the transferrin receptor serves as a delivery vehicle for effective brain targeting: Initial applications in anti-HIV antisense drug delivery to the brain. J. Immunol. 1999, 163, 4421–4426.
[208]
Ng, P.P.; Dela Cruz, J.S.; Sorour, D.N.; Stinebaugh, J.M.; Shin, S.-U.; Shin, D.S.; Morrison, S.L.; Penichet, M.L. An anti-transferrin receptor-avidin fusion protein exhibits both strong proapoptotic activity and the ability to deliver various molecules into cancer cells. Proc. Natl. Acad. Sci. USA 2002, 99, 10706–10711, doi:10.1073/pnas.162362999.
[209]
Xuan, C.; Steward, K.K.; Timmerman, J.M.; Morrison, S.L. Targeted delivery of interferon-alpha via fusion to anti-CD20 results in potent antitumor activity against B-cell lymphoma. Blood 2010, 115, 2864–2871, doi:10.1182/blood-2009-10-250555.
[210]
Koehn, T.A.; Trimble, L.L.; Alderson, K.L.; Erbe, A.K.; McDowell, K.A.; Grzywacz, B.; Hank, J.A.; Sondel, P.M. Increasing the clinical efficacy of NK and antibody-mediated cancer immunotherapy: Potential predictors of successful clinical outcome based on observations in high-risk neuroblastoma. Front. Pharmacol. 2012, 3, 91.
[211]
Lode, H.N.; Xiang, R.; Becker, J.C.; Gillies, S.D.; Reisfel, R.A. Immunocytokines: A promising approach to cancer immunotherapy. Pharmacol. Ther. 1998, 80, 277–292, doi:10.1016/S0163-7258(98)00033-3.
Dela Cruz, J.S.; Ryan Trinh, K.; Morrison, S.L.; Penichet, M.L. Recombinant anti-human HER2/neu IgG3-(GM-CSF) fusion protein retains antigen specificity and cytokine function and demonstrates antitumor activity. J. Immunol. 2000, 165, 5112–5121.
[214]
Cho, H.M.; Rosenblatt, J.D.; Kang, Y.-S.; Luisa Iruela-Arispe, M.; Morrison, S.L.; Penichet, M.L.; Kwon, Y.-G.; Kim, T.-W.; Webster, K.A.; Nechustan, H. Enhanced inhibition of murine tumor and human breast tumor xenografts using targeted delivery of an antibody-endostatin fusion protein. Mol. Cancer Ther. 2005, 4, 956–967.
[215]
Zhang, H.; Lu, S.; Morrison, S.L.; Tomlinson, S. Targeting of functional antibody-decay-accelerating factor fusion proteins to a cell surface. J. Biol. Chem. 2001, 276, 27290–27295, doi:10.1074/jbc.M100436200.
[216]
Fung, V.P. Method for producing recombinant proteins. US Patent 7,294,481, 2007.
[217]
Sassenfeld, H.M.; Remmele, R.L., Jr.; McCoy, R.E. Increased recovery of active proteins. US Patent 7,157,55, 2007.
[218]
Bouchon, A.; Facchetti, F.; Weigand, M.A.; Colonna, M. TREM-1 amplifies inflammation and is a crucial mediator of septic shock. Nature 2001, 410, 1103–1107, doi:10.1038/35074114.
[219]
Iwai, H.; Kohsaka, H. Blockade of Triggering receptor expressed on myeloid cells-1 as a new therapy of arthritis. Nihon Rinsho Meneki Gakkai Kaishi 2012, 35, 81–86, doi:10.2177/jsci.35.81.
[220]
Holash, J.; Davis, S.; Papadopoulos, N.; Croll, S.D.; Ho, L.; Russell, M.; Boland, P.; Leidich, R.; Hylton, D.; Burova, E.; et al. VEGF-Trap: A VEGF blocker with potent antitumor effects. Proc. Natl. Acad. Sci. USA 2002, 99, 11393–11398, doi:10.1073/pnas.172398299.
[221]
Peters, R.T.; Low, S.C.; Kamphaus, G.D.; Dumont, J.A.; Amari, J.V.; Lu, Q.; Zarbis-Papastoitsis, G.; Reidy, T.J.; Merricks, E.P.; Nichols, T.C.; et al. Prolonged activity of factor IX as a monomeric Fc fusion protein. Blood 2010, 115, 2057–2064, doi:10.1182/blood-2009-08-239665.
[222]
Hall, M.P.; Gegg, C.; Walker, K.; Spahr, C.; Ortiz, R.; Patel, V.; Yu, S.; Zhang, L.; Lu, H.; DeSilva, B.; et al. Ligand-binding mass spectrometry to study biotransformation of fusion protein drugs and guide immunoassay development: Strategic approach and application to peptibodies targeting the thrombopoietin receptor. AAPS J. 2010, 12, 576–585, doi:10.1208/s12248-010-9218-9.
[223]
Gokarn, Y.R.; Matthew Fesinmeyer, R.; Saluja, A.; Cao, S.; Dankberg, J.; Goetze, A.; Remmele, R.L., Jr.; Narhi, L.O.; Brems, D.N. Ion-specific modulation of protein interactions: Anion-induced, reversible oligomerization of a fusion protein. Protein Sci. 2009, 18, 169–179.
[224]
Nisonoff, A.; Rivers, M.M. Recombination of a mixture of univalent antibody fragments of different specificity. Arch. Biochem. Biophys. 1961, 93, 460–462, doi:10.1016/0003-9861(61)90296-X.
[225]
May, C.; Sapra, P.; Gerber, H.P. Advances in bispecific biotherapeutics for the treatment of cancer. Biochem. Pharmacol. 2012, 84, 1105–1112, doi:10.1016/j.bcp.2012.07.011.
[226]
Scott, A.M.; Wolchok, J.D.; Old, L.J. Antibody therapy of cancer. Nat. Rev. Cancer 2012, 12, 278–287, doi:10.1038/nrc3236.
[227]
Vallera, D.A.; Todhunter, D.A.; Kuroki, D.W.; Shu, Y.; Sicheneder, A.; Chen, H. A bispecific recombinant immunotoxin, DT2219, targeting human CD19 and CD22 receptors in a mouse xenograft model of B-cell leukemia/lymphoma. Clin. Cancer Res. 2005, 11, 3879–3888, doi:10.1158/1078-0432.CCR-04-2290.
[228]
Dorvillius, M.; Garambois, V.; Pourquier, D.; Gutowski, M.; Rouanet, P.; Mani, J.-C.; Pugnière, M.; Hynes, N.E.; Pèlegrin, A. Targeting of human breast cancer by a bispecific antibody directed against two tumour-associated antigens: ErbB-2 and carcinoembryonic antigen. Tumour Biol. 2002, 23, 337–347, doi:10.1159/000069793.
[229]
Jimenez, X.; Lu, D.; Brennan, L.; Persaud, K.; Liu, M.; Miao, H.; Witte, L.; Zhu, Z. A recombinant, fully human, bispecific antibody neutralizes the biological activities mediated by both vascular endothelial growth factor receptors 2 and 3. Mol. Cancer Ther. 2005, 4, 427–434.
[230]
Lu, D.; Zhang, H.; Koo, H.; Tonra, J.; Balderes, P.; Prewett, M.; Corcoran, E.; Mangalampalli, V.; Bassi, R.; Anselma, D.; et al. 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. 2005, 280, 19665–19672, doi:10.1074/jbc.M500815200.
[231]
Tanaka, K.; Isselbacher, K.J.; Khoury, G.; Jay, G. Reversal of oncogenesis by the expression of a major histocompatibility complex class I gene. Science 1985, 228, 26–30.
[232]
Hartmann, F.; Renner, C.; Jung, W.; Deisting, C.; Juwana, M.; Eichentopf, B.; Kloft, M.; Pfreundschuh, M. Treatment of refractory Hodgkin's disease with an anti-CD16/CD30 bispecific antibody. Blood 1997, 89, 2042–2047.
Reinagel, M.L.; Taylor, R.P. Transfer of immune complexes from erythrocyte CR1 to mouse macrophages. J. Immunol. 2000, 164, 1977–1985.
[235]
French, R.R.; Penney, C.A.; Browning, A.C.; Stirpe, F.; George, A.J.; Glennie, M.J. Delivery of the ribosome-inactivating protein, gelonin, to lymphoma cells via CD22 and CD38 using bispecific antibodies. Br. J. Cancer 1995, 71, 986–994, doi:10.1038/bjc.1995.190.
[236]
Ford, C.H.; Osborne, P.A.; Rego, B.G.; Mathew, A. Bispecific antibody targeting of doxorubicin to carcinoembryonic antigen-expressing colon cancer cell lines in vitro and in vivo. Int. J. Cancer 2001, 92, 851–855, doi:10.1002/ijc.1262.
[237]
Zhu, H.; Jain, R.K.; Baxter, L.T. Tumor pretargeting for radioimmunodetection and radioimmunotherapy. J. Nucl. Med. 1998, 39, 65–76.
[238]
Kipriyanov, S.M.; Le Gall, F. Recent advances in the generation of bispecific antibodies for tumor immunotherapy. Curr. Opin. Drug Discov. Develop. 2004, 7, 233–242.
[239]
Mack, M.; Riethmuller, G.; Kufer, P. A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity. Proc. Natl. Acad. Sci. USA 1995, 92, 7021–7025, doi:10.1073/pnas.92.15.7021.
[240]
Mack, M.; Gruber, R.; Schmidt, S.; Riethmüller, G.; Kufer, P. Biologic properties of a bispecific single-chain antibody directed against 17-1A (EpCAM) and CD3: Tumor cell-dependent T cell stimulation and cytotoxic activity. J. Immunol. 1997, 158, 3965–39670.
[241]
Milstein, C.; Cuello, A.C. Hybrid hybridomas and their use in immunohistochemistry. Nature 1983, 305, 537–540, doi:10.1038/305537a0.
[242]
Staerz, U.D.; Bevan, M.J. Hybrid hybridoma producing a bispecific monoclonal antibody that can focus effector T-cell activity. Proc. Natl. Acad. Sci. USA 1986, 83, 1453–1457, doi:10.1073/pnas.83.5.1453.
[243]
Lindhofer, H.; Mocikat, R.; Steipe, B.; Thierfelder, S. Preferential species-restricted heavy/light chain pairing in rat/mouse quadromas. Implications for a single-step purification of bispecific antibodies. J. Immunol. 1995, 155, 219–225.
[244]
Brennan, M.; Davison, P.F.; Paulus, H. Preparation of bispecific antibodies by chemical recombination of monoclonal immunoglobulin G1 fragments. Science 1985, 229, 81–83.
[245]
Merchant, A.M.; Zhu, Z.; Yuan, J.Q.; Goddard, A.; Adams, C.W.; Presta, L.G.; Carter, P. An efficient route to human bispecific IgG. Nat. Biotechnol. 1998, 16, 677–681, doi:10.1038/nbt0798-677.
[246]
Ridgway, J.B.; Presta, L.G.; Carter, P. 'Knobs-into-holes' engineering of antibody CH3 domains for heavy chain heterodimerization. Protein Eng. 1996, 9, 617–621, doi:10.1093/protein/9.7.617.
[247]
Davis, J.H.; Aperlo, C.; Li, Y.; Kurosawa, E.; Lan, Y.; Lo, K.-M.; Huston, J.S. SEEDbodies: Fusion proteins based on strand-exchange engineered domain (SEED) CH3 heterodimers in an Fc analogue platform for asymmetric binders or immunofusions and bispecific antibodies. Protein Eng. Des. Sel. 2010, 23, 195–202, doi:10.1093/protein/gzp094.
[248]
Holliger, P.; Prospero, T.; Winter, G. "Diabodies": Small bivalent and bispecific antibody fragments. Proc. Natl. Acad. Sci. USA 1993, 90, 6444–6448, doi:10.1073/pnas.90.14.6444.
[249]
Kipriyanov, S.M.; Moldenhauer, G.; Schuhmacher, J.; Cochlovius, B.; Von der Lieth, C.-W.; Ronald Matys, E.; Little, M. Bispecific tandem diabody for tumor therapy with improved antigen binding and pharmacokinetics. J. Mol. Biol. 1999, 293, 41–56, doi:10.1006/jmbi.1999.3156.
[250]
De Jonge, J.; Heirman, C.; de Veerman, M.; Van Meirvenne, S.; Moser, M.; Leo, O.; Thielemans, K. In vivo retargeting of T cell effector function by recombinant bispecific single chain Fv (anti-CD3 x anti-idiotype) induces long-term survival in the murine BCL1 lymphoma model. J. Immunol. 1998, 161, 1454–1461.
[251]
Kufer, P.; Lutterbuse, R.; Baeuerle, P.A. A revival of bispecific antibodies. Trends Biotechnol. 2004, 22, 238–244, doi:10.1016/j.tibtech.2004.03.006.
[252]
Topp, M.S.; Kufer, P.; G？kbuget, N.; Goebeler, M.; Klinger, M.; Neumann, S.; Horst, H.-A.; Raff, T.; Viardot, A.; Schmid, M.; et al. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J. Clin. Oncol. 2011, 29, 2493–2498, doi:10.1200/JCO.2010.32.7270.
[253]
Baeuerle, P.A.; Reinhardt, C. Bispecific T-cell engaging antibodies for cancer therapy. Cancer Res. 2009, 69, 4941–4944, doi:10.1158/0008-5472.CAN-09-0547.
[254]
Johnson, S.; Burke, S.; Huang, L.; Gorlatov, S.; Li, H.; Wang, W.; Zhang, W.; Tuaillon, N.; Rainey, J.; Barat, B.; et al. 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. 2010, 399, 436–449, doi:10.1016/j.jmb.2010.04.001.
Wu, C.; Ying, H.; Grinnell, C.; Bryant, S.; Miller, R.; Clabbers, A.; Bose, S.; McCarthy, D.; Zhu, R.-R.; Santora, L.; et al. Simultaneous targeting of multiple disease mediators by a dual-variable-domain immunoglobulin. Nat. Biotechnol. 2007, 25, 1290–1297, doi:10.1038/nbt1345.
[257]
F-star. Available online: www.f-star.com (accessed on 1 June 2013).
[258]
IMMUNOCORE. Available online: www.immunocore.com (accessed on 1 June 2013).
[259]
Hartmann, F.; Renner, C.; Jung, W.; da Costa, L.; Tembrink, S.; Held, G.; Sek, A.; K？nig, J.; Bauer, S.; Kloft, M.; Pfreundschuh, M. Anti-CD16/CD30 bispecific antibody treatment for Hodgkin's disease: Role of infusion schedule and costimulation with cytokines. Clin. Cancer Res. 2001, 7, 1873–1881.
[260]
Schmitt, M.; Schmitt, A.; Reinhardt, P.; Thess, B.; Manfras, B.; Lindhofer, H.; Riechelmann, H.; Wiesneth, M.; Gronau, S. Opsonization with a trifunctional bispecific (alphaCD3 x alphaEpCAM) antibody results in efficient lysis in vitro and in vivo of EpCAM positive tumor cells by cytotoxic T lymphocytes. Int. J. Oncol. 2004, 25, 841–848.
[261]
Jager, M.; Schoberth, A.; Ruf, P.; Hess, J.; Hennig, M.; Schmalfeldt, B.; Wimberger, P.; Str？hlein, M.; Theissen, B.; Heiss, M.M.; et al. Immunomonitoring results of a phase II/III study of malignant ascites patients treated with the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3). Cancer Res. 2012, 72, 24–32, doi:10.1158/0008-5472.CAN-11-2235.
[262]
Pluen, A.; Boucher, Y.; Ramanujan, S.; McKee, T.D.; Gohongi, T.; di Tomaso, E.; Brown, E.B.; Izumi, Y.; Campbell, R.B.; Berk, D.A.; et al. Role of tumor-host interactions in interstitial diffusion of macromolecules: Cranial vs. subcutaneous tumors. Proc. Natl. Acad. Sci. USA 2001, 98, 4628–4633, doi:10.1073/pnas.081626898.
[263]
Khawli, L.A.; Biela, B.; Hu, P.; Epstein, A.L. Comparison of recombinant derivatives of chimeric TNT-3 antibody for the radioimaging of solid tumors. Hybrid. Hybridomics 2003, 22, 1–9, doi:10.1089/153685903321538026.
[264]
Tahtis, K.; Lee, F.-T.; Smyth, F.E.; Power, B.E.; Renner, C.; Brechbiel, M.W.; Old, L.J.; Hudson, P.J.; Scott, A.M. Biodistribution properties of (111)indium-labeled C-functionalized trans-cyclohexyl diethylenetriaminepentaacetic acid humanized 3S193 diabody and F(ab')(2) constructs in a breast carcinoma xenograft model. Clin. Cancer Res. 2001, 7, 1061–1072.
[265]
Thurber, G.M.; Wittrup, K.D. Quantitative spatiotemporal analysis of antibody fragment diffusion and endocytic consumption in tumor spheroids. Cancer Res. 2008, 68, 3334–3341, doi:10.1158/0008-5472.CAN-07-3018.
[266]
Ottiger, M.; Thiel, M.A.; Feige, U.; Lichtlen, P.; Urech, D.M. Efficient intraocular penetration of topical anti-TNF-alpha single-chain antibody (ESBA105) to anterior and posterior segment without penetration enhancer. Invest. Ophthalmol. Vis. Sci. 2009, 50, 779–786.
[267]
Cardoso, R.M.; Zwick, M.B.; Stanfield, R.L.; Kunert, R.; Binley, J.M.; Katinger, H.; Burton, D.R. Broadly neutralizing anti-HIV antibody 4E10 recognizes a helical conformation of a highly conserved fusion-associated motif in gp41. Immunity 2005, 22, 163–173, doi:10.1016/j.immuni.2004.12.011.
[268]
Stijlemans, B.; Wyns, L.; Senter, P.; Revets, H.; De Baetselier, P.; Muyldermans, S.; Magez, S. Efficient targeting of conserved cryptic epitopes of infectious agents by single domain antibodies. African trypanosomes as paradigm. J. Biol. Chem. 2004, 279, 1256–1261.
[269]
Nuttall, S.D.; Humberstone, K.S.; Krishnan, U.V.; Carmichael, J.A.; Doughty, L.; Hattarki, M.; Coley, A.M.; Casey, J.L.; Anders, R.F.; Foley, M.; et al. Selection and affinity maturation of IgNAR variable domains targeting Plasmodium falciparum AMA1. Proteins 2004, 55, 187–197, doi:10.1002/prot.20005.
[270]
Streltsov, V.A.; Varghese, J.N.; Carmichael, J.A.; Irving, R.A.; Hudson, P.J.; Nuttall, S.D. Structural evidence for evolution of shark Ig new antigen receptor variable domain antibodies from a cell-surface receptor. Proc. Natl. Acad. Sci. USA 2004, 101, 12444–12449.
Chen, W.; Dimitrov, D.S. Human monoclonal antibodies and engineered antibody domains as HIV-1 entry inhibitors. Curr. Opin. HIV AIDS 2009, 4, 112–117, doi:10.1097/COH.0b013e328322f95e.
[273]
Holliger, P.; Hudson, P.J. Engineered antibody fragments and the rise of single domains. Nat. Biotechnol. 2005, 23, 1126–1136, doi:10.1038/nbt1142.
[274]
Albrecht, H.; Burke, P.A.; Natarajan, A.; Xiong, C.-Y.; Kalicinsky, M.; DeNardo, G.L.; DeNardo, S.J. Production of soluble ScFvs with C-terminal-free thiol for site-specific conjugation or stable dimeric ScFvs on demand. Bioconjug. Chem. 2004, 15, 16–26, doi:10.1021/bc030018+.
[275]
Lu, D.; Jimenez, X.; Zhanga, H.; Atkins, A.; Brennanb, L.; Balderes, P.; Bohlend, P.; Witte, L.; Zhu, Z. Di-diabody: A novel tetravalent bispecific antibody molecule by design. J. Immunol. Methods 2003, 279, 219–232, doi:10.1016/S0022-1759(03)00251-5.
[276]
Robinson, M.K.; Doss, M.; Shaller, C.; Narayanan, D.; Marks, J.D.; Adler, L.P.; González Trotter, D.E.; Adams, G.P. Quantitative immuno-positron emission tomography imaging of HER2-positive tumor xenografts with an iodine-124 labeled anti-HER2 diabody. Cancer Res. 2005, 65, 1471–1478, doi:10.1158/0008-5472.CAN-04-2008.
Brignole, C.; Pastorino, F.; Marimpietri, D.; Pagnan, G.; Pistorio, A.; Allen, T.M.; Pistoia, V.; Ponzoni, M. Immune cell-mediated antitumor activities of GD2-targeted liposomal c-myb antisense oligonucleotides containing CpG motifs. J. Natl. Cancer Inst. 2004, 96, 1171–1180, doi:10.1093/jnci/djh221.
[281]
van Broekhoven, C.L.; Parish, C.R.; Demange, C.; Britton, W.J.; Altin, J.G. Targeting dendritic cells with antigen-containing liposomes: A highly effective procedure for induction of antitumor immunity and for tumor immunotherapy. Cancer Res. 2004, 64, 4357–4365, doi:10.1158/0008-5472.CAN-04-0138.
[282]
Sharma, S.K.; Barbara Pedley, R.; Bhatia, J.; Boxer, G.M.; El-Emir, E.; Qureshi, U.; Tolner, B.; Lowe, H.; Paul Michael, N.; Minton, N.; et al. Sustained tumor regression of human colorectal cancer xenografts using a multifunctional mannosylated fusion protein in antibody-directed enzyme prodrug therapy. Clin. Cancer Res. 2005, 11, 814–825.
[283]
Cortez-Retamozo, V.; Backmann, N.; Senter, P.D.; Wernery, U.; De Baetselier, P.; Muyldermans, S.; Revets, H. Efficient cancer therapy with a nanobody-based conjugate. Cancer Res. 2004, 64, 2853–2857, doi:10.1158/0008-5472.CAN-03-3935.
Ryckaert, S.; Pardon, E.; Steyaert, J.; Callewaert, N. Isolation of antigen-binding camelid heavy chain antibody fragments (nanobodies) from an immune library displayed on the surface of Pichia pastoris. J. Biotechnol. 2010, 145, 93–98, doi:10.1016/j.jbiotec.2009.10.010.
[286]
Muyldermans, S.; Baral, T.N.; Cortez Retamozzo, V.; De Baetselier, P.; De Genst, E.; Kinnec, J.; Leonhardt, H.; Magez, S.; Nguyen, V.K.; Revets, H.; et al. Camelid immunoglobulins and nanobody technology. Vet. Immunol. Immunopathol. 2009, 128, 178–183, doi:10.1016/j.vetimm.2008.10.299.
[287]
Vandenbroucke, K.; de Haard, H.; Beirnaert, E.; Dreier, T.; Lauwereys, M.; Huyck, L.; Van Huysse, J.; Demetter, P.; Steidler, L.; Remaut, E.; et al. Orally administered L. lactis secreting an anti-TNF Nanobody demonstrate efficacy in chronic colitis. Mucosal. Immunol. 2010, 3, 49–56, doi:10.1038/mi.2009.116.
[288]
Sanz, L.; Blanco, B.; Alvarez-Vallina, L. Antibodies and gene therapy: Teaching old 'magic bullets' new tricks. Trends Immunol. 2004, 25, 85–91, doi:10.1016/j.it.2003.12.001.
[289]
Afanasieva, T.A.; Wittmer, M.; Vitaliti, A.; Ajmo, M.; Neri, D.; Klemenz, R. Single-chain antibody and its derivatives directed against vascular endothelial growth factor: Application for antiangiogenic gene therapy. Gene Ther. 2003, 10, 1850–1859, doi:10.1038/sj.gt.3302085.
[290]
Blanco, B.; Holliger, P.; Vile, R.G.; álvarez-Vallina, L. 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. 2003, 171, 1070–1077.
[291]
Jendreyko, N.; Popkov, M.; Beerli, R.R.; Chung, J.; McGavern, D.B.; Rader, C.; Barbas, C.F., III. Intradiabodies, bispecific, tetravalent antibodies for the simultaneous functional knockout of two cell surface receptors. J. Biol. Chem. 2003, 278, 47812–47819.
[292]
Grosse-Hovest, L.; Wick, W.; Minoia, R.; Weller, M.; Rammensee, H.-G.; Brem, G.; Jung, G. Supraagonistic, bispecific single-chain antibody purified from the serum of cloned, transgenic cows induces T-cell-mediated killing of glioblastoma cells in vitro and in vivo. Int. J. Cancer 2005, 117, 1060–1064, doi:10.1002/ijc.21294.
Keck, Z.Y.; Li, S.H.; Xia, J.; von Hahn, T.; Balfe, P.; McKeating, J.A.; Witteveldt, J.; Patel, A.H.; Alter, H.; Rice, C.M.; et al. Mutations in hepatitis C virus E2 located outside the CD81 binding sites lead to escape from broadly neutralizing antibodies but compromise virus infectivity. J. Virol. 2009, 83, 6149–6160, doi:10.1128/JVI.00248-09.
[296]
Zharikova, D.; Mozdzanowska, K.; Feng, J.; Zhang, M.; Gerhard, W. Influenza type A virus escape mutants emerge in vivo in the presence of antibodies to the ectodomain of matrix protein 2. J. Virol. 2005, 79, 6644–6654, doi:10.1128/JVI.79.11.6644-6654.2005.
[297]
Prabakaran, M.; Prabhu, N.; He, F.; Qian, H.; Ho, H.-T.; Qiang, J.; Meng, T.; Goutama, M.; Kwang, J. Combination therapy using chimeric monoclonal antibodies protects mice from lethal H5N1 infection and prevents formation of escape mutants. PLoS One 2009, 4, e5672.
[298]
Haurum, J.S. Recombinant human polyclonal antibodies: A new class of therapeutic antibodies against viral infections. Curr. Pharm. Des. 2006, 12, 2007–2015, doi:10.2174/138161206777442173.
[299]
de Kruif, J.; Bakker, A.B.H.; Marissen, W.E.; Arjen Kramer, R.; Throsby, M.; Rupprecht, C.E.; Goudsmit, J. A human monoclonal antibody cocktail as a novel component of rabies postexposure prophylaxis. Annu. Rev. Med. 2007, 58, 359–368, doi:10.1146/annurev.med.58.061705.145053.
[300]
Elliott, E.V.; Pindar, A.; Stevenson, F.K.; Stevenson, G.T. Synergistic cytotoxic effects of antibodies directed against different cell surface determinants. Immunology 1978, 34, 405–409.
[301]
Hellstrom, I.; Brown, J.P.; Hellstrom, K.E. Monoclonal antibodies to two determinants of melanoma-antigen p97 act synergistically in complement-dependent cytotoxicity. J. Immunol. 1981, 127, 157–160.
[302]
Ziegler-Heitbrock, H.W.; Reiter, C.; Trenkmann, J.; Fütterer, A.; Riethmüller, G. Protection of mice against tetanus toxin by combination of two human monoclonal antibodies recognizing distinct epitopes on the toxin molecule. Hybridoma (Larchmt) 1986, 5, 21–31, doi:10.1089/hyb.1986.5.21.
[303]
Bakker, A.B.; Python, C.; Kissling, C.J.; Pandyad, P.; Marissen, W.E.; Brinka, M.F.; Lagerwerf, F.; Worsta, S.; van Corven, E.; Kostense, S.; et al. First administration to humans of a monoclonal antibody cocktail against rabies virus: Safety, tolerability, and neutralizing activity. Vaccine 2008, 26, 5922–5927, doi:10.1016/j.vaccine.2008.08.050.
[304]
Mascola, J.R.; Louder, M.K.; VanCott, T.C.; Sapan, C.V.; Lambert, J.S.; Muenz, L.R.; Bunow, B.; Birx, D.L.; Robb, M.L. Potent and synergistic neutralization of human immunodeficiency virus (HIV) type 1 primary isolates by hyperimmune anti-HIV immunoglobulin combined with monoclonal antibodies 2F5 and 2G12. J. Virol. 1997, 71, 7198–7206.
[305]
Armbruster, C.; Stiegler, G.M.; Vcelar, B.A.; J？ger, W.; K？ller, U.; Jilch, R.; Ammann, C.G.; Pruenster, M.; Stoiber, H.; Katinger, H.W.D. Passive immunization with the anti-HIV-1 human monoclonal antibody (hMAb) 4E10 and the hMAb combination 4E10/2F5/2G12. J. Antimicrob. Chemother. 2004, 54, 915–920, doi:10.1093/jac/dkh428.
[306]
Trkola, A.; Kuster, H.; Rusert, P.; Joos, B.; Fischer, M.; Leemann, C.; Manrique, A.; Huber, M.; Rehr, M.; Oxenius, A.; et al. Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies. Nat. Med. 2005, 11, 615–622, doi:10.1038/nm1244.
[307]
Spiridon, C.I.; Ghetie, M.-A.; Uhr, J.; Marches, R.; Li, J.-L.; Shen, G.-L.; Vitetta, E.S. Targeting multiple Her-2 epitopes with monoclonal antibodies results in improved antigrowth activity of a human breast cancer cell line in vitro and in vivo. Clin. Cancer Res. 2002, 8, 1720–1730.
[308]
Strauss, S.J.; Morschhauser, F.; Rech, J.; Repp, R.; Solal-Celigny, P.; Zinzani, P.L.; Engert, A.; Coiffier, B.; Hoelzer, D.F.; Wegener, W.A.; et al. Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J. Clin. Oncol. 2006, 24, 3880–3886, doi:10.1200/JCO.2006.05.6291.
[309]
Nowakowski, A.; Wang, C.; Powers, D.B.; Amersdorfer, P.; Smith, T.J.; Montgomery, V.A.; Sheridan, R.; Blake, R.; Smith, L.A.; Marks, J.D. Potent neutralization of botulinum neurotoxin by recombinant oligoclonal antibody. Proc. Natl. Acad. Sci. USA 2002, 99, 11346–11350, doi:10.1073/pnas.172229899.
[310]
Jefferis, R. Glycosylation of recombinant antibody therapeutics. Biotechnol. Prog. 2005, 21, 11–16, doi:10.1021/bp040016j.
[311]
Burton, D.R.; Desrosiers, R.C.; Doms, R.W.; Koff, W.C.; Kwong, P.D.; Moore, J.P.; Nabel, G.J.; Sodronski, J.; Wilson, I.A.; Wyatt, R. HIV vaccine design and the neutralizing antibody problem. Nat. Immunol. 2004, 5, 233–236, doi:10.1038/ni0304-233.
[312]
Marasco, W.A.; Sui, J. The growth and potential of human antiviral monoclonal antibody therapeutics. Nat. Biotechnol. 2007, 25, 1421–1434, doi:10.1038/nbt1363.
[313]
Milestones in Microbiology; 1556–1940; Brock, T.D., Ed.; ASM Press: Washington DC, USA, 1998.
[314]
Casadevall, A.; Scharff, M.D. Serum therapy revisited: Animal models of infection and development of passive antibody therapy. Antimicrob. Agents Chemother. 1994, 38, 1695–1702, doi:10.1128/AAC.38.8.1695.
[315]
Logtenberg, T. Antibody cocktails: Next-generation biopharmaceuticals with improved potency. Trends Biotechnol. 2007, 25, 390–394, doi:10.1016/j.tibtech.2007.07.005.
[316]
Glassy, M.C.; McKnight, M. The rate-limiting step in obtaining human monoclonal antibody drug pharmaceuticals. Expert Opin. Investig. Drugs 1995, 4, 225–228, doi:10.1517/13543784.4.3.225.
