Advertisement

Protein & Cell

, Volume 1, Issue 4, pp 319–330 | Cite as

Monoclonal antibodies — a proven and rapidly expanding therapeutic modality for human diseases

  • Zhiqiang AnEmail author
Review
First Online:

Abstract

The study of antibodies has been a focal point in modern biology and medicine since the early 1900s. However, progress in therapeutic antibody development was slow and intermittent until recently. The first antibody therapy, murine-derived murononab OKT3 for acute organ rejection, was approved by the US Food and Drug Administration (FDA) in 1986, more than a decade after César Milstein and Georges Köhler developed methods for the isolation of mouse monoclonal antibodies from hybridoma cells in 1975. As a result of the scientific, technological, and clinical breakthroughs in the 1980s and 1990s, the pace of therapeutic antibody discovery and development accelerated. Antibodies are becoming a major drug modality with more than two dozen therapeutic antibodies in the clinic and hundreds more in development. Despite the progress, need for improvement exists at every level. Antibody therapeutics provides fertile ground for protein scientists to fulfill the dream of personalized medicine through basic scientific discovery and technological innovation.

Keywords

monoclonal antibodies personalized medicine therapeutic antibodies 
Download to read the full article text

References

  1. Albanell, J., and Baselga, J. (1999). Trastuzumab, a humanized anti-HER2 monoclonal antibody, for the treatment of breast cancer. Drugs Today (Barc) 35, 931–946.Google Scholar
  2. An, Z. (2009). Therapeutic monoclonal antibodies: from bench to clinic, Hoboken, NJ: John Wiley and Sons.CrossRefGoogle Scholar
  3. An, Z., Forrest, G., Moore, R., Cukan, M., Haytko, P., Huang, L., Vitelli, S., Zhao, J.Z., Lu, P., Hua, J., et al. (2009). IgG2m4, an engineered antibody isotype with reduced Fc function. MAbs 1, 572–579.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Arnold, J.N., Wormald, M.R., Sim, R.B., Rudd, P.M., and Dwek, R.A. (2007). The impact of glycosylation on the biological function and structure of human immunoglobulins. Annu Rev Immunol 25, 21–50.CrossRefPubMedGoogle Scholar
  5. Bender, N.K., Heilig, C.E., Dröll, B., Wohlgemuth, J., Armbruster, F.P., and Heilig, B. (2007). Immunogenicity, efficacy and adverse events of adalimumab in RA patients. Rheumatol Int 27, 269–274.CrossRefPubMedGoogle Scholar
  6. Bostrom, J., Yu, S.F., Kan, D., Appleton, B.A., Lee, C.V., Billeci, K., Man, W., Peale, F., Ross, S., Wiesmann, C., et al. (2009). Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site. Science 323, 1610–1614.CrossRefPubMedGoogle Scholar
  7. Carter, P.J. (2006). Potent antibody therapeutics by design. Nat Rev Immunol 6, 343–357.CrossRefPubMedGoogle Scholar
  8. Chen, S., Yu, L., Jiang, C., Zhao, Y., Sun, D., Li, S., Liao, G., Chen, Y., Fu, Q., Tao, Q., et al. (2005). Pivotal study of iodine-131-labeled chimeric tumor necrosis treatment radioimmunotherapy in patients with advanced lung cancer. J Clin Oncol 23, 1538–1547.CrossRefPubMedGoogle Scholar
  9. Chua, Y.J., and Cunningham, D. (2006). Panitumumab. Drugs Today (Barc) 42, 711–719.CrossRefGoogle Scholar
  10. Cohen, D.J., Benvenisty, A.I., Cianci, J., and Hardy, M.A. (1989). OKT3 prophylaxis in cadaveric kidney transplant recipients with delayed graft function. Am J Kidney Dis 14, 19–27.PubMedGoogle Scholar
  11. Cohenuram, M., and Saif, M.W. (2007). Panitumumab the first fully human monoclonal antibody: from the bench to the clinic. Anticancer Drugs 18, 7–15.CrossRefPubMedGoogle Scholar
  12. Cox, K.M., Sterling, J.D., Regan, J.T., Gasdaska, J.R., Frantz, K.K., Peele, C.G., Black, A., Passmore, D., Moldovan-Loomis, C., Srinivasan, M., et al. (2006). Glycan optimization of a human monoclonal antibody in the aquatic plant Lemna minor. Nat Biotechnol 24, 1591–1597.CrossRefPubMedGoogle Scholar
  13. Davies, A.J. (2004). Tositumomab and iodine [131I] tositumomab in the management of follicular lymphoma. iAn oncologist’s view. Q J Nucl Med Mol Imaging 48, 305–316.PubMedGoogle Scholar
  14. Ducry, L., and Stump, B. (2010). Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies. Bioconjug Chem 21, 5–13.CrossRefPubMedGoogle Scholar
  15. Ehrlich, P. (1908). Partial cell functions—Nobel lecture, December 11, 1908 in Physiology or Medicine: including presentation speeches and laureates’ biographies. Amsterdam, 1967: Elsevier Publisher.Google Scholar
  16. Enever, C., Batuwangala, T., Plummer, C., and Sepp, A. (2009). Next generation immunotherapeutics—honing the magic bullet. Curr Opin Biotechnol 20, 405–411.CrossRefPubMedGoogle Scholar
  17. Faulds, D., and Sorkin, E.M. (1994). Abciximab (c7E3 Fab). A review of its pharmacology and therapeutic potential in ischaemic heart disease. Drugs 48, 583–598.CrossRefPubMedGoogle Scholar
  18. Feldhaus, M.J., Siegel, R.W., Opresko, L.K., Coleman, J.R., Feldhaus, J.M., Yeung, Y.A., Cochran, J.R., Heinzelman, P., Colby, D., Swers, J., et al. (2003). Flow-cytometric isolation of human antibodies from a nonimmune Saccharomyces cerevisiae surface display library. Nat Biotechnol 21, 163–170.CrossRefPubMedGoogle Scholar
  19. Ferrajoli, A., O’Brien, S., and Keating, M.J. (2001). Alemtuzumab: a novel monoclonal antibody. Expert Opin Biol Ther 1, 1059–1065.CrossRefPubMedGoogle Scholar
  20. Gaza-Bulseco, G., Faldu, S., Hurkmans, K., Chumsae, C., and Liu, H. (2008). Effect of methionine oxidation of a recombinant monoclonal antibody on the binding affinity to protein A and protein G. J Chromatogr B Analyt Technol Biomed Life Sci 870, 55–62.CrossRefPubMedGoogle Scholar
  21. Gauvreau, G.M., Becker, A.B., Boulet, L.P., Chakir, J., Fick, R.B., Greene, W.L., Killian, K.J., O’Byrne P, M., Reid, J.K., and Cockcroft, D.W. (2003). The effects of an anti-CD11a mAb, efalizumab, on allergen-induced airway responses and airway inflammation in subjects with atopic asthma. J Allergy Clin Immunol 112, 331–338.CrossRefPubMedGoogle Scholar
  22. Hanes, J., Jermutus, L., Weber-Bornhauser, S., Bosshard, H.R., and Plückthun, A. (1998). Ribosome display efficiently selects and evolves high-affinity antibodies in vitro from immune libraries. Proc Natl Acad Sci U S A 95, 14130–14135.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Harvey, B.R., Georgiou, G., Hayhurst, A., Jeong, K.J., Iverson, B.L., and Rogers, G.K. (2004). Anchored periplasmic expression, a versatile technology for the isolation of high-affinity antibodies from Escherichia coli-expressed libraries. Proc Natl Acad Sci U S A 101, 9193–9198.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Holliger, P., and Hudson, P.J. (2005). Engineered antibody fragments and the rise of single domains. Nat Biotechnol 23, 1126–1136.CrossRefPubMedGoogle Scholar
  25. Holt, L.J., Herring, C., Jespers, L.S., Woolven, B.P., and Tomlinson, I. M. (2003). Domain antibodies: proteins for therapy. Trends Biotechnol 21, 484–490.CrossRefPubMedGoogle Scholar
  26. Hoogenboom, H.R. (2005). Selecting and screening recombinant antibody libraries. Nat Biotechnol 23, 1105–1116.CrossRefPubMedGoogle Scholar
  27. Huang, L., Lu, J., Wroblewski, V.J., Beals, J.M., and Riggin, R.M. (2005). In vivo deamidation characterization of monoclonal antibody by LC/MS/MS. Anal Chem 77, 1432–1439.CrossRefPubMedGoogle Scholar
  28. Jakobovits, A., Amado, R.G., Yang, X., Roskos, L., and Schwab, G. (2007). From XenoMouse technology to panitumumab, the first fully human antibody product from transgenic mice. Nat Biotechnol 25, 1134–1143.CrossRefPubMedGoogle Scholar
  29. James, L.C., Roversi, P., and Tawfik, D.S. (2003). Antibody multispecificity mediated by conformational diversity. Science 299, 1362–1367.CrossRefPubMedGoogle Scholar
  30. Jin, A., Ozawa, T., Tajiri, K., Obata, T., Kondo, S., Kinoshita, K., Kadowaki, S., Takahashi, K., Sugiyama, T., Kishi, H., et al. (2009). A rapid and efficient single-cell manipulation method for screening antigen-specific antibody-secreting cells from human peripheral blood. Nat Med 15, 1088–1092.CrossRefPubMedGoogle Scholar
  31. Kaneko, Y., Nimmerjahn, F., and Ravetch, J.V. (2006). Antiinflammatory activity of immunoglobulin G resulting from Fc sialylation. Science 313, 670–673.CrossRefPubMedGoogle Scholar
  32. Kenneth, T.E., and Kertes, P.J. (2006). Ranibizumab in neovascular age-related macular degeneration. Clin Interv Aging 1, 451–466.CrossRefPubMedGoogle Scholar
  33. Kerr, D.J. (2004). Targeting angiogenesis in cancer: clinical development of bevacizumab. Nat Clin Pract Oncol 1, 39–43.CrossRefPubMedGoogle Scholar
  34. Kettleborough, C.A., Saldanha, J., Heath, V.J., Morrison, C.J., and Bendig, M.M. (1991). Humanization of a mouse monoclonal antibody by CDR-grafting: the importance of framework residues on loop conformation. Protein Eng 4, 773–783.CrossRefPubMedGoogle Scholar
  35. Keating, M.J., Dritselis, A., Yasothan, U., and Kirkpatrick, P. (2010). Ofatumumab. Nat Rev Drug Discov 9, 101–102.CrossRefPubMedGoogle Scholar
  36. Kies, M.S., and Harari, P.M. (2002). Cetuximab (Imclone/Merck/Bristol-Myers Squibb). Curr Opin Investig Drugs 3, 1092–1100.PubMedGoogle Scholar
  37. Köhler, G., and Milstein, C. (1975). Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256, 495–497.CrossRefPubMedGoogle Scholar
  38. Krasner, C., and Joyce, R.M. (2001). Zevalin: 90yttrium labeled anti-CD20 (ibritumomab tiuxetan), a new treatment for non-Hodgkin’s lymphoma. Curr Pharm Biotechnol 2, 341–349.CrossRefPubMedGoogle Scholar
  39. Kufer, P., Lutterbüse, R., and Baeuerle, P.A. (2004). A revival of bispecific antibodies. Trends Biotechnol 22, 238–244.CrossRefPubMedGoogle Scholar
  40. Kwakkenbos, M.J., Diehl, S.A., Yasuda, E., Bakker, A.Q., van Geelen, C.M., Lukens, M.V., van Bleek, G.M., Widjojoatmodjo, M.N., Bogers, W.M., Mei, H., et al. (2010). Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming. Nat Med 16, 123–128.CrossRefPubMedGoogle Scholar
  41. Lee, C.M., Iorno, N., Sierro, F., and Christ, D. (2007). Selection of human antibody fragments by phage display. Nat Protoc 2, 3001–3008.CrossRefPubMedGoogle Scholar
  42. Li, H., Sethuraman, N., Stadheim, T.A., Zha, D., Prinz, B., Ballew, N., Bobrowicz, P., Choi, B.K., Cook, W.J., Cukan, M., et al. (2006a). Optimization of humanized IgGs in glycoengineered Pichia pastoris. Nat Biotechnol 24, 210–215.CrossRefPubMedGoogle Scholar
  43. Li, J., Sai, T., Berger, M., Chao, Q., Davidson, D., Deshmukh, G., Drozdowski, B., Ebel, W., Harley, S., Henry, M., et al. (2006b). Human antibodies for immunotherapy development generated via a human B cell hybridoma technology. Proc Natl Acad Sci U S A 103, 3557–3562.CrossRefPubMedPubMedCentralGoogle Scholar
  44. Lin, S., Shen, Z., Zha, D., Sharkey, N., Prinz, B., Hamilton, S., Pavoor, T.V., Bobrowicz, B., Shaikh, S.S., Rittenhour, A.M., et al. (2010). Selection of Pichia pastoris strains expressing recombinant immunoglobulin G by cell surface labeling. J Immunol Methods.Google Scholar
  45. Lonberg, N. (2005). Human antibodies from transgenic animals. Nat Biotechnol 23, 1117–1125.CrossRefPubMedGoogle Scholar
  46. Maloney, D.G., Grillo-Lopez, A.J., White, C.A., Bodkin, D., Schilder, R.J., Neidhart, J.A., Janakiraman, N., Foon, K.A., Liles, T.M., Dallaire, B.K., et al. (1997). IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood 90, 2188–2195.PubMedGoogle Scholar
  47. Mimura, Y., Jefferis, R., Mimura-Kimura, Y., Abrahams, J., and Rudd, P.M. (2009). Glycosylation of Therapeutic IgGs. In Therapeutic Monoclonal Antibodies: from Bench to Clinic, An, Z. (ed), pp 67–89. Hoboken, NJ: John Wiley and Sons, Inc.CrossRefGoogle Scholar
  48. Morrison, S.L., Johnson, M.J., Herzenberg, L.A., and Oi, V.T. (1984). Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc Natl Acad Sci U S A 81, 6851–6855.CrossRefPubMedPubMedCentralGoogle Scholar
  49. Nashan, B., Moore, R., Amlot, P., Schmidt, A.G., Abeywickrama, K., and Soulillou, J.P. (1997). Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group. Lancet 350, 1193–1198.CrossRefPubMedGoogle Scholar
  50. Nelson, A.L., and Reichert, J.M. (2009). Development trends for therapeutic antibody fragments. Nat Biotechnol 27, 331–337.CrossRefPubMedGoogle Scholar
  51. News (2010). Deal watch: BMS acquires rights for IL-6 inhibitor. Nat Rev Drug Discov 9, 10.Google Scholar
  52. Ogunniyi, A.O., Story, C.M., Papa, E., Guillen, E., and Love, J.C. (2009). Screening individual hybridomas by microengraving to discover monoclonal antibodies. Nat Protoc 4, 767–782.CrossRefPubMedPubMedCentralGoogle Scholar
  53. Onrust, S.V., and Lamb, H.M. (1998). Infliximab: a review of its use in Crohn’s disease and rheumatoid arthritis. BioDrugs 10, 397–422.CrossRefPubMedGoogle Scholar
  54. Pappas, D.A., Bathon, J.M., Hanicq, D., Yasothan, U., and Kirkpatrick, P. (2009). Golimumab. Nat Rev Drug Discov 8, 695–696.CrossRefPubMedGoogle Scholar
  55. Paul-Pletzer, K. (2006). Tocilizumab: blockade of interleukin-6 signaling pathway as a therapeutic strategy for inflammatory disorders. Drugs Today (Barc) 42, 559–576.CrossRefGoogle Scholar
  56. Pedersen, M.W., Jacobsen, H.J., Koefoed, K., Hey, A., Pyke, C., Haurum, J.S., and Kragh, M. (2010). Sym004: a novel synergistic anti-epidermal growth factor receptor antibody mixture with superior anticancer efficacy. Cancer Res 70, 588–597.CrossRefPubMedGoogle Scholar
  57. Peipp, M., Lammerts van Bueren, J.J., Schneider-Merck, T., Bleeker, W.W., Dechant, M., Beyer, T., Repp, R., van Berkel, P.H., Vink, T., van de Winkel, J.G., et al. (2008). Antibody fucosylation differentially impacts cytotoxicity mediated by NK and PMN effector cells. Blood 112, 2390–2399.CrossRefPubMedGoogle Scholar
  58. Reichert, J.M., and Valge-Archer, V.E. (2007). Development trends for monoclonal antibody cancer therapeutics. Nat Rev Drug Discov 6, 349–356.CrossRefPubMedGoogle Scholar
  59. Rothe, C., Urlinger, S., Lohning, C., Prassler, J., Stark, Y., Jager, U., Hubner, B., Bardroff, M., Pradel, I., Boss, M., et al. (2007). The human combinatorial antibody library HuCAL GOLD combines diversification of all six CDRs according to the natural immune system with a novel display method for efficient selection of highaffinity antibodies. J Mol Biol 376, 1182–1200.CrossRefPubMedGoogle Scholar
  60. Rother, R.P., Rollins, S.A., Mojcik, C.F., Brodsky, R.A., and Bell, L. (2007). Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol 25, 1256–1264.CrossRefPubMedGoogle Scholar
  61. Rudick, R.A., and Sandrock, A. (2004). Natalizumab: alpha 4-integrin antagonist selective adhesion molecule inhibitors for MS. Expert Rev Neurother 4, 571–580.CrossRefPubMedGoogle Scholar
  62. Russell, N.D., Corvalan, J.R., Gallo, M.L., Davis, C.G., and Pirofski, L. (2000). Production of protective human antipneumococcal antibodies by transgenic mice with human immunoglobulin loci. Infect Immun 68, 1820–1826.CrossRefPubMedPubMedCentralGoogle Scholar
  63. Rutgeerts P, Schreiber S, Feagan B, Keininger D.L., O’Neil L., Fedorak R.N. (2007) Certolizumab pegol, a monthly subcutaneously administered Fc-free anti-TNFalpha, improves healthrelated quality of life in patients with moderate to severe Crohn’s disease. Int J Colorectal Dis 23, 289–296.CrossRefPubMedPubMedCentralGoogle Scholar
  64. Sandborn, W.J., Feagan, B.G., Stoinov, S., Honiball, P.J., Rutgeerts, P., Mason, D., Bloomfield, R., Schreiber, S., and the PRECISE 1 Study Investigators. (2007). Certolizumab pegol for the treatment of Crohn’s disease. N Engl J Med 357, 228–238.CrossRefPubMedGoogle Scholar
  65. Scheid, J.F., Mouquet, H., Feldhahn, N., Seaman, M.S., Velinzon, K., Pietzsch, J., Ott, R.G., Anthony, R.M., Zebroski, H., Hurley, A., et al. (2009). Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature 458, 636–640.CrossRefPubMedGoogle Scholar
  66. Smith, E.S., and Zauderer, M. (2009) Antibody selection from immunoglobulin libraries expressed in mammalian cells. In therapeutic monoclonal antibodies: from bench to clinic, An, Z. (ed), pp 283–307. Hoboken, NJ: John Wiley & Sons.CrossRefGoogle Scholar
  67. Smith, K., Garman, L., Wrammert, J., Zheng, N.Y., Capra, J.D., Ahmed, R., and Wilson, P.C. (2009). Rapid generation of fully human monoclonal antibodies specific to a vaccinating antigen. Nat Protoc 4, 372–384.CrossRefPubMedPubMedCentralGoogle Scholar
  68. Sorokin, P. (2000). Mylotarg approved for patients with CD33 + acute myeloid leukemia. Clin J Oncol Nurs 4, 279–280.PubMedGoogle Scholar
  69. Stanfield, R.L., and Wilson, I.A. (2009). Antibody molecular structure. In therapeutic monoclonal antibodies: from bench to clinic, An, Z. (ed), pp 889. Hoboken, NJ: John Wiley & Sons, Inc.Google Scholar
  70. Stangel, M., and Pul, R. (2006). Basic principles of intravenous immunoglobulin (IVIg) treatment. J Neurol 253, V18–24.CrossRefPubMedGoogle Scholar
  71. Storch, G.A. (1998). Humanized monoclonal antibody for prevention of respiratory syncytial virus infection. Pediatrics 102, 648–651.CrossRefPubMedGoogle Scholar
  72. Strohl, W.R. (2009). Therapeutic monoclonal antibodies: past, present, and future. In therapeutic monoclonal antibodies: from bench to clinic, An, Z. (ed), pp 889. Hoboken, NJ: John Wiley & Sons, Inc.Google Scholar
  73. Thistlethwaite, J.R. Jr, Haag, B.W., Gaber, A.O., Stuart, J.K., Aronson, A.J., Mayes, J.T., Lloyd, D.M., and Stuart, F.P. (1987). The use of OKT3 to treat steroid-resistant renal allograft rejection in patients receiving cyclosporine. Transplant Proc 19, 1901–1904.PubMedGoogle Scholar
  74. Traggiai, E., Becker, S., Subbarao, K., Kolesnikova, L., Uematsu, Y., Gismondo, M.R., Murphy, B.R., Rappuoli, R., and Lanzavecchia, A. (2004). An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus. Nat Med 10, 871–875.CrossRefPubMedGoogle Scholar
  75. Van Bockstaele, F., Holz, J.B., and Revets, H. (2009). The development of nanobodies for therapeutic applications. Curr Opin Investig Drugs 10, 1212–1224.PubMedGoogle Scholar
  76. Vaughan, T.J., Williams, A.J., Pritchard, K., Osbourn, J.K., Pope, A. R., Earnshaw, J.C., McCafferty, J., Hodits, R.A., Wilton, J., and Johnson, K.S. (1996). Human antibodies with sub-nanomolar affinities isolated from a large non-immunized phage display library. Nat Biotechnol 14, 309–314.CrossRefPubMedGoogle Scholar
  77. Vincenti, F., Kirkman, R., Light, S., Bumgardner, G., Pescovitz, M., Halloran, P., Neylan, J., Wilkinson, A., Ekberg, H., Gaston, R., et al. (1998). Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. N Engl J Med 338, 161–165.CrossRefPubMedGoogle Scholar
  78. Walker, L.M., Phogat, S.K., Chan-Hui, P.Y., Wagner, D., Phung, P., Goss, J.L., Wrin, T., Simek, M.D., Fling, S., Mitcham, J.L., et al. (2009). Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 326, 285–289.CrossRefPubMedPubMedCentralGoogle Scholar
  79. Wang, Y., Washabaugh, M.W., and Zhao, Q.J. (2009). Characterization of heterogeneity in monoclonal antibody products. In characterization of heterogeneity in monoclonal antibody products, An, Z. (ed), pp 541–554. Hoboken, NJ: John Wiley and Sons.Google Scholar
  80. Weinblatt, M.E., Keystone, E.C., Furst, D.E., Moreland, L.W., Weisman, M.H., Birbara, C.A., Teoh, L.A., Fischkoff, S.A., and Chartash, E.K. (2003). Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum 48, 35–45.CrossRefPubMedGoogle Scholar
  81. Winau, F., Westphal, O., and Winau, R. (2004). Paul Ehrlich-in search of the magic bullet. Microbes Infect 6, 786–789.CrossRefPubMedGoogle Scholar
  82. Wrammert, J., Smith, K., Miller, J., Langley, W.A., Kokko, K., Larsen, C., Zheng, N.Y., Mays, I., Garman, L., Helms, C., et al. (2008). Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature 453, 667–671.CrossRefPubMedPubMedCentralGoogle Scholar
  83. Wu, C., Ying, H., Grinnell, C., Bryant, S., Miller, R., Clabbers, A., Bose, S., McCarthy, D., Zhu, R.R., Santora, L., et al. (2007). Simultaneous targeting of multiple disease mediators by a dualvariable-domain immunoglobulin. Nat Biotechnol 25, 1290–1297.CrossRefPubMedGoogle Scholar
  84. Yu, Y.L., Lee, P., Ke, Y.H., Zhang, Y.K., Yu, Q., Lee, J., Li, M.Z., Song, J.L., Chen, J.G., Dai, J.H., et al. (2010). A humanized anti-VEGF rabbit monoclonal antibody inhibits angiogenesis and blocks tumor growth in xenograft models. PLoS One 5, e9072.CrossRefPubMedPubMedCentralGoogle Scholar
  85. Zhu, L., van de Lavoir, M.C., Albanese, J., Beenhouwer, D.O., Cardarelli, P.M., Cuison, S., Deng, D.F., Deshpande, S., Diamond, J. H., Green, L., et al. (2005). Production of human monoclonal antibody in eggs of chimeric chickens. Nat Biotechnol 23, 1159–1169.CrossRefPubMedGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  1. 1.Brown Foundation Institute of Molecular MedicineUniversity of Texas Health Science Center at HoustonHoustonUSA

Personalised recommendations