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. 2010 Apr 1;1(4):319–330. doi: 10.1007/s13238-010-0052-8

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

Zhiqiang An 1,
PMCID: PMC4875100  PMID: 21203944

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

References

  1. Albanell J., Baselga J. Trastuzumab, a humanized anti-HER2 monoclonal antibody, for the treatment of breast cancer. Drugs Today (Barc) 1999;35:931–946. [PubMed] [Google Scholar]
  2. An Z. Therapeutic monoclonal antibodies: from bench to clinic. Hoboken, NJ: John Wiley and Sons; 2009. [Google 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. IgG2m4, an engineered antibody isotype with reduced Fc function. MAbs. 2009;1:572–579. doi: 10.4161/mabs.1.6.10185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Arnold J.N., Wormald M.R., Sim R.B., Rudd P.M., Dwek R.A. The impact of glycosylation on the biological function and structure of human immunoglobulins. Annu Rev Immunol. 2007;25:21–50. doi: 10.1146/annurev.immunol.25.022106.141702. [DOI] [PubMed] [Google Scholar]
  5. Bender N.K., Heilig C.E., Dröll B., Wohlgemuth J., Armbruster F.P., Heilig B. Immunogenicity, efficacy and adverse events of adalimumab in RA patients. Rheumatol Int. 2007;27:269–274. doi: 10.1007/s00296-006-0183-7. [DOI] [PubMed] [Google 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. Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site. Science. 2009;323:1610–1614. doi: 10.1126/science.1165480. [DOI] [PubMed] [Google Scholar]
  7. Carter P.J. Potent antibody therapeutics by design. Nat Rev Immunol. 2006;6:343–357. doi: 10.1038/nri1837. [DOI] [PubMed] [Google Scholar]
  8. Chen S., Yu L., Jiang C., Zhao Y., Sun D., Li S., Liao G., Chen Y., Fu Q., Tao Q., et al. Pivotal study of iodine-131-labeled chimeric tumor necrosis treatment radioimmunotherapy in patients with advanced lung cancer. J Clin Oncol. 2005;23:1538–1547. doi: 10.1200/JCO.2005.06.108. [DOI] [PubMed] [Google Scholar]
  9. Chua Y.J., Cunningham D. Panitumumab. Drugs Today (Barc) 2006;42:711–719. doi: 10.1358/dot.2006.42.11.1032061. [DOI] [PubMed] [Google Scholar]
  10. Cohen D.J., Benvenisty A.I., Cianci J., Hardy M.A. OKT3 prophylaxis in cadaveric kidney transplant recipients with delayed graft function. Am J Kidney Dis. 1989;14:19–27. [PubMed] [Google Scholar]
  11. Cohenuram M., Saif M.W. Panitumumab the first fully human monoclonal antibody: from the bench to the clinic. Anticancer Drugs. 2007;18:7–15. doi: 10.1097/CAD.0b013e32800feecb. [DOI] [PubMed] [Google 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. Glycan optimization of a human monoclonal antibody in the aquatic plant Lemna minor. Nat Biotechnol. 2006;24:1591–1597. doi: 10.1038/nbt1260. [DOI] [PubMed] [Google Scholar]
  13. Davies A.J. Tositumomab and iodine [131I] tositumomab in the management of follicular lymphoma. iAn oncologist’s view. Q J Nucl Med Mol Imaging. 2004;48:305–316. [PubMed] [Google Scholar]
  14. Ducry L., Stump B. Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies. Bioconjug Chem. 2010;21:5–13. doi: 10.1021/bc9002019. [DOI] [PubMed] [Google 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.
  16. Enever C., Batuwangala T., Plummer C., Sepp A. Next generation immunotherapeutics—honing the magic bullet. Curr Opin Biotechnol. 2009;20:405–411. doi: 10.1016/j.copbio.2009.07.002. [DOI] [PubMed] [Google Scholar]
  17. Faulds D., Sorkin E.M. Abciximab (c7E3 Fab). A review of its pharmacology and therapeutic potential in ischaemic heart disease. Drugs. 1994;48:583–598. doi: 10.2165/00003495-199448040-00007. [DOI] [PubMed] [Google 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. Flow-cytometric isolation of human antibodies from a nonimmune Saccharomyces cerevisiae surface display library. Nat Biotechnol. 2003;21:163–170. doi: 10.1038/nbt785. [DOI] [PubMed] [Google Scholar]
  19. Ferrajoli A., O’Brien S., Keating M.J. Alemtuzumab: a novel monoclonal antibody. Expert Opin Biol Ther. 2001;1:1059–1065. doi: 10.1517/14712598.1.6.1059. [DOI] [PubMed] [Google Scholar]
  20. Gaza-Bulseco G., Faldu S., Hurkmans K., Chumsae C., Liu H. 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. 2008;870:55–62. doi: 10.1016/j.jchromb.2008.05.045. [DOI] [PubMed] [Google 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., Cockcroft D.W. 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. 2003;112:331–338. doi: 10.1067/mai.2003.1689. [DOI] [PubMed] [Google Scholar]
  22. Hanes J., Jermutus L., Weber-Bornhauser S., Bosshard H.R., Plückthun A. Ribosome display efficiently selects and evolves high-affinity antibodies in vitro from immune libraries. Proc Natl Acad Sci U S A. 1998;95:14130–14135. doi: 10.1073/pnas.95.24.14130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Harvey B.R., Georgiou G., Hayhurst A., Jeong K.J., Iverson B.L., Rogers G.K. 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. 2004;101:9193–9198. doi: 10.1073/pnas.0400187101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Holliger P., Hudson P.J. Engineered antibody fragments and the rise of single domains. Nat Biotechnol. 2005;23:1126–1136. doi: 10.1038/nbt1142. [DOI] [PubMed] [Google Scholar]
  25. Holt L.J., Herring C., Jespers L.S., Woolven B.P., Tomlinson I. M. Domain antibodies: proteins for therapy. Trends Biotechnol. 2003;21:484–490. doi: 10.1016/j.tibtech.2003.08.007. [DOI] [PubMed] [Google Scholar]
  26. Hoogenboom H.R. Selecting and screening recombinant antibody libraries. Nat Biotechnol. 2005;23:1105–1116. doi: 10.1038/nbt1126. [DOI] [PubMed] [Google Scholar]
  27. Huang L., Lu J., Wroblewski V.J., Beals J.M., Riggin R.M. In vivo deamidation characterization of monoclonal antibody by LC/MS/MS. Anal Chem. 2005;77:1432–1439. doi: 10.1021/ac0494174. [DOI] [PubMed] [Google Scholar]
  28. Jakobovits A., Amado R.G., Yang X., Roskos L., Schwab G. From XenoMouse technology to panitumumab, the first fully human antibody product from transgenic mice. Nat Biotechnol. 2007;25:1134–1143. doi: 10.1038/nbt1337. [DOI] [PubMed] [Google Scholar]
  29. James L.C., Roversi P., Tawfik D.S. Antibody multispecificity mediated by conformational diversity. Science. 2003;299:1362–1367. doi: 10.1126/science.1079731. [DOI] [PubMed] [Google Scholar]
  30. Jin A., Ozawa T., Tajiri K., Obata T., Kondo S., Kinoshita K., Kadowaki S., Takahashi K., Sugiyama T., Kishi H., et al. A rapid and efficient single-cell manipulation method for screening antigen-specific antibody-secreting cells from human peripheral blood. Nat Med. 2009;15:1088–1092. doi: 10.1038/nm.1966. [DOI] [PubMed] [Google Scholar]
  31. Kaneko Y., Nimmerjahn F., Ravetch J.V. Antiinflammatory activity of immunoglobulin G resulting from Fc sialylation. Science. 2006;313:670–673. doi: 10.1126/science.1129594. [DOI] [PubMed] [Google Scholar]
  32. Kenneth T.E., Kertes P.J. Ranibizumab in neovascular age-related macular degeneration. Clin Interv Aging. 2006;1:451–466. doi: 10.2147/ciia.2006.1.4.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kerr D.J. Targeting angiogenesis in cancer: clinical development of bevacizumab. Nat Clin Pract Oncol. 2004;1:39–43. doi: 10.1038/ncponc0026. [DOI] [PubMed] [Google Scholar]
  34. Kettleborough C.A., Saldanha J., Heath V.J., Morrison C.J., Bendig M.M. Humanization of a mouse monoclonal antibody by CDR-grafting: the importance of framework residues on loop conformation. Protein Eng. 1991;4:773–783. doi: 10.1093/protein/4.7.773. [DOI] [PubMed] [Google Scholar]
  35. Keating M.J., Dritselis A., Yasothan U., Kirkpatrick P. Ofatumumab. Nat Rev Drug Discov. 2010;9:101–102. doi: 10.1038/nrd3100. [DOI] [PubMed] [Google Scholar]
  36. Kies M.S., Harari P.M. Cetuximab (Imclone/Merck/Bristol-Myers Squibb) Curr Opin Investig Drugs. 2002;3:1092–1100. [PubMed] [Google Scholar]
  37. Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  38. Krasner C., Joyce R.M. Zevalin: 90yttrium labeled anti-CD20 (ibritumomab tiuxetan), a new treatment for non-Hodgkin’s lymphoma. Curr Pharm Biotechnol. 2001;2:341–349. doi: 10.2174/1389201013378545. [DOI] [PubMed] [Google Scholar]
  39. Kufer P., Lutterbüse R., Baeuerle P.A. A revival of bispecific antibodies. Trends Biotechnol. 2004;22:238–244. doi: 10.1016/j.tibtech.2004.03.006. [DOI] [PubMed] [Google 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. Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming. Nat Med. 2010;16:123–128. doi: 10.1038/nm.2071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Lee C.M., Iorno N., Sierro F., Christ D. Selection of human antibody fragments by phage display. Nat Protoc. 2007;2:3001–3008. doi: 10.1038/nprot.2007.448. [DOI] [PubMed] [Google 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. Optimization of humanized IgGs in glycoengineered Pichia pastoris. Nat Biotechnol. 2006;24:210–215. doi: 10.1038/nbt1178. [DOI] [PubMed] [Google Scholar]
  43. Li J., Sai T., Berger M., Chao Q., Davidson D., Deshmukh G., Drozdowski B., Ebel W., Harley S., Henry M., et al. Human antibodies for immunotherapy development generated via a human B cell hybridoma technology. Proc Natl Acad Sci U S A. 2006;103:3557–3562. doi: 10.1073/pnas.0511285103. [DOI] [PMC free article] [PubMed] [Google 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. [DOI] [PubMed]
  45. Lonberg N. Human antibodies from transgenic animals. Nat Biotechnol. 2005;23:1117–1125. doi: 10.1038/nbt1135. [DOI] [PubMed] [Google 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. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood. 1997;90:2188–2195. [PubMed] [Google Scholar]
  47. Mimura Y., Jefferis R., Mimura-Kimura Y., Abrahams J., Rudd P.M. Glycosylation of Therapeutic IgGs. In: An Z., editor. Therapeutic Monoclonal Antibodies: from Bench to Clinic. Hoboken, NJ: John Wiley and Sons, Inc.; 2009. pp. 67–89. [Google Scholar]
  48. Morrison S.L., Johnson M.J., Herzenberg L.A., Oi V.T. Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc Natl Acad Sci U S A. 1984;81:6851–6855. doi: 10.1073/pnas.81.21.6851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Nashan B., Moore R., Amlot P., Schmidt A.G., Abeywickrama K., Soulillou J.P. Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group. Lancet. 1997;350:1193–1198. doi: 10.1016/S0140-6736(97)09278-7. [DOI] [PubMed] [Google Scholar]
  50. Nelson A.L., Reichert J.M. Development trends for therapeutic antibody fragments. Nat Biotechnol. 2009;27:331–337. doi: 10.1038/nbt0409-331. [DOI] [PubMed] [Google Scholar]
  51. News Deal watch: BMS acquires rights for IL-6 inhibitor. Nat Rev Drug Discov. 2010;9:10. doi: 10.1038/nrd3094. [DOI] [PubMed] [Google Scholar]
  52. Ogunniyi A.O., Story C.M., Papa E., Guillen E., Love J.C. Screening individual hybridomas by microengraving to discover monoclonal antibodies. Nat Protoc. 2009;4:767–782. doi: 10.1038/nprot.2009.40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Onrust S.V., Lamb H.M. Infliximab: a review of its use in Crohn’s disease and rheumatoid arthritis. BioDrugs. 1998;10:397–422. doi: 10.2165/00063030-199810050-00006. [DOI] [PubMed] [Google Scholar]
  54. Pappas D.A., Bathon J.M., Hanicq D., Yasothan U., Kirkpatrick P. Golimumab. Nat Rev Drug Discov. 2009;8:695–696. doi: 10.1038/nrd2982. [DOI] [PubMed] [Google Scholar]
  55. Paul-Pletzer K. Tocilizumab: blockade of interleukin-6 signaling pathway as a therapeutic strategy for inflammatory disorders. Drugs Today (Barc) 2006;42:559–576. doi: 10.1358/dot.2006.42.9.1025692. [DOI] [PubMed] [Google Scholar]
  56. Pedersen M.W., Jacobsen H.J., Koefoed K., Hey A., Pyke C., Haurum J.S., Kragh M. Sym004: a novel synergistic anti-epidermal growth factor receptor antibody mixture with superior anticancer efficacy. Cancer Res. 2010;70:588–597. doi: 10.1158/0008-5472.CAN-09-1417. [DOI] [PubMed] [Google 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. Antibody fucosylation differentially impacts cytotoxicity mediated by NK and PMN effector cells. Blood. 2008;112:2390–2399. doi: 10.1182/blood-2008-03-144600. [DOI] [PubMed] [Google Scholar]
  58. Reichert J.M., Valge-Archer V.E. Development trends for monoclonal antibody cancer therapeutics. Nat Rev Drug Discov. 2007;6:349–356. doi: 10.1038/nrd2241. [DOI] [PubMed] [Google Scholar]
  59. Rothe C., Urlinger S., Lohning C., Prassler J., Stark Y., Jager U., Hubner B., Bardroff M., Pradel I., Boss M., et al. 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. 2007;376:1182–1200. doi: 10.1016/j.jmb.2007.12.018. [DOI] [PubMed] [Google Scholar]
  60. Rother R.P., Rollins S.A., Mojcik C.F., Brodsky R.A., Bell L. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol. 2007;25:1256–1264. doi: 10.1038/nbt1344. [DOI] [PubMed] [Google Scholar]
  61. Rudick R.A., Sandrock A. Natalizumab: alpha 4-integrin antagonist selective adhesion molecule inhibitors for MS. Expert Rev Neurother. 2004;4:571–580. doi: 10.1586/14737175.4.4.571. [DOI] [PubMed] [Google Scholar]
  62. Russell N.D., Corvalan J.R., Gallo M.L., Davis C.G., Pirofski L. Production of protective human antipneumococcal antibodies by transgenic mice with human immunoglobulin loci. Infect Immun. 2000;68:1820–1826. doi: 10.1128/IAI.68.4.1820-1826.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Rutgeerts P., Schreiber S., Feagan B., Keininger D.L., O’Neil L., Fedorak R.N. 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. 2007;23:289–296. doi: 10.1007/s00384-007-0395-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Sandborn W.J., Feagan B.G., Stoinov S., Honiball P.J., Rutgeerts P., Mason D., Bloomfield R., Schreiber S., the PRECISE 1 Study Investigators Certolizumab pegol for the treatment of Crohn’s disease. N Engl J Med. 2007;357:228–238. doi: 10.1056/NEJMoa067594. [DOI] [PubMed] [Google 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. Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature. 2009;458:636–640. doi: 10.1038/nature07930. [DOI] [PubMed] [Google Scholar]
  66. Smith E.S., Zauderer M. Antibody selection from immunoglobulin libraries expressed in mammalian cells. In: An Z., editor. therapeutic monoclonal antibodies: from bench to clinic. Hoboken, NJ: John Wiley & Sons; 2009. pp. 283–307. [Google Scholar]
  67. Smith K., Garman L., Wrammert J., Zheng N.Y., Capra J.D., Ahmed R., Wilson P.C. Rapid generation of fully human monoclonal antibodies specific to a vaccinating antigen. Nat Protoc. 2009;4:372–384. doi: 10.1038/nprot.2009.3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Sorokin P. Mylotarg approved for patients with CD33 + acute myeloid leukemia. Clin J Oncol Nurs. 2000;4:279–280. [PubMed] [Google Scholar]
  69. Stanfield R.L., Wilson I.A. Antibody molecular structure. In: An Z., editor. therapeutic monoclonal antibodies: from bench to clinic. Hoboken, NJ: John Wiley & Sons, Inc; 2009. p. 889. [Google Scholar]
  70. Stangel M., Pul R. Basic principles of intravenous immunoglobulin (IVIg) treatment. J Neurol. 2006;253:V18–24. doi: 10.1007/s00415-006-5003-1. [DOI] [PubMed] [Google Scholar]
  71. Storch G.A. Humanized monoclonal antibody for prevention of respiratory syncytial virus infection. Pediatrics. 1998;102:648–651. doi: 10.1542/peds.102.3.648. [DOI] [PubMed] [Google Scholar]
  72. Strohl W.R. Therapeutic monoclonal antibodies: past, present, and future. In: An Z., editor. therapeutic monoclonal antibodies: from bench to clinic. Hoboken, NJ: John Wiley & Sons, Inc.; 2009. p. 889. [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., Stuart F.P. The use of OKT3 to treat steroid-resistant renal allograft rejection in patients receiving cyclosporine. Transplant Proc. 1987;19:1901–1904. [PubMed] [Google Scholar]
  74. Traggiai E., Becker S., Subbarao K., Kolesnikova L., Uematsu Y., Gismondo M.R., Murphy B.R., Rappuoli R., Lanzavecchia A. An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus. Nat Med. 2004;10:871–875. doi: 10.1038/nm1080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Van Bockstaele F., Holz J.B., Revets H. The development of nanobodies for therapeutic applications. Curr Opin Investig Drugs. 2009;10:1212–1224. [PubMed] [Google 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., Johnson K.S. Human antibodies with sub-nanomolar affinities isolated from a large non-immunized phage display library. Nat Biotechnol. 1996;14:309–314. doi: 10.1038/nbt0396-309. [DOI] [PubMed] [Google Scholar]
  77. Vincenti F., Kirkman R., Light S., Bumgardner G., Pescovitz M., Halloran P., Neylan J., Wilkinson A., Ekberg H., Gaston R., et al. Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. N Engl J Med. 1998;338:161–165. doi: 10.1056/NEJM199801153380304. [DOI] [PubMed] [Google 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. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science. 2009;326:285–289. doi: 10.1126/science.1178746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Wang Y., Washabaugh M.W., Zhao Q.J. Characterization of heterogeneity in monoclonal antibody products. In: An Z., editor. characterization of heterogeneity in monoclonal antibody products. Hoboken, NJ: John Wiley and Sons; 2009. pp. 541–554. [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., Chartash E.K. 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. 2003;48:35–45. doi: 10.1002/art.10697. [DOI] [PubMed] [Google Scholar]
  81. Winau F., Westphal O., Winau R. Paul Ehrlich-in search of the magic bullet. Microbes Infect. 2004;6:786–789. doi: 10.1016/j.micinf.2004.04.003. [DOI] [PubMed] [Google 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. Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature. 2008;453:667–671. doi: 10.1038/nature06890. [DOI] [PMC free article] [PubMed] [Google 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. Simultaneous targeting of multiple disease mediators by a dualvariable-domain immunoglobulin. Nat Biotechnol. 2007;25:1290–1297. doi: 10.1038/nbt1345. [DOI] [PubMed] [Google 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. A humanized anti-VEGF rabbit monoclonal antibody inhibits angiogenesis and blocks tumor growth in xenograft models. PLoS One. 2010;5:e9072. doi: 10.1371/journal.pone.0009072. [DOI] [PMC free article] [PubMed] [Google 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. Production of human monoclonal antibody in eggs of chimeric chickens. Nat Biotechnol. 2005;23:1159–1169. doi: 10.1038/nbt1132. [DOI] [PubMed] [Google Scholar]

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