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Protein & Cell

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ISSN 1674-8018(Online)

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Prot Cell    2010, Vol. 1 Issue (4) : 319-330    https://doi.org/10.1007/s13238-010-0052-8      PMID: 21203944
REVIEW
Monoclonal antibodies – a proven and rapidly expanding therapeutic modality for human diseases
Zhiqiang An()
Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
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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 K?hler 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     
Corresponding Author(s): An Zhiqiang,Email:Zhiqiang.an@uth.tmc.edu   
Issue Date: 01 April 2010
 Cite this article:   
Zhiqiang An. Monoclonal antibodies – a proven and rapidly expanding therapeutic modality for human diseases[J]. Prot Cell, 2010, 1(4): 319-330.
 URL:  
https://academic.hep.com.cn/pac/EN/10.1007/s13238-010-0052-8
https://academic.hep.com.cn/pac/EN/Y2010/V1/I4/319
Fig.1  Diagrams of various antibody structures.
A) A generic IgG molecule. (B) A scFv fragment. (C) A Fab fragment. (D) A F(ab’)2 fragment. (E) A mouse IgG molecule. (F) A murine:human chimeric IgG molecule. (G) A humanized IgG molecule. (H) A human IgG molecule.
Fig.1  Diagrams of various antibody structures.
A) A generic IgG molecule. (B) A scFv fragment. (C) A Fab fragment. (D) A F(ab’)2 fragment. (E) A mouse IgG molecule. (F) A murine:human chimeric IgG molecule. (G) A humanized IgG molecule. (H) A human IgG molecule.
Fig.2  History of antibody therapeutics.
Green boxes represent scientific and technology milestones. Blue boxes are antibody therapeutics developed as a result of the scientific and technology breakthroughs.
Fig.2  History of antibody therapeutics.
Green boxes represent scientific and technology milestones. Blue boxes are antibody therapeutics developed as a result of the scientific and technology breakthroughs.
generic nametrade namemanufacturerlaunch datetherapy areamajor indicationtargetprotein form/isotypedeliveryreference
MuromonabOrthoclone/OKT3Johnson & Johnson1986AIIDtransplant rejectionCD3murine IgG2aIVCohen et al., 1989
AbciximabReoProEli Lilly1995CVcardiovascular diseaseCD41chimeric FabIVFaulds and Sorkin, 1994
RituximabRituxan/MabTheraGenentech/Roche1997oncologyNon-Hodgkin’s lymphomaCD20chimeric IgG1IVMaloney et al., 1997
DaclizumabZenapaxRoche1997AIIDtransplant rejectionCD25humanized IgG1IVVincenti et al., 1998
BasiliximabSimulectNovartis1998AIIDtransplant rejectionCD25chimeric IgG1IVNashan et al., 1997
InfliximabRemicadeCentocor1998AIIDrheumatoid arthritisTNF alphachimeric IgG1IVOnrust and Lamb, 1998
PalivizumabSynagisMedImmune1998IDrespiratory syncytial virusRSV F-proteinchimeric IgG1IMStorch, 1998
TrastuzumabHerceptinGenentech1998oncologybreast cancerHer2humanized IgG1IVAlbanell and Baselga, 1999
Gemtuzumab/ozogamicinMylotargWyeth2000oncologyacute myelogenous leukemiaCD33humanized IgG4 conjugated with ozogamicinIVSorokin, 2000
AlemtuzumabCampathBayer-Schering2001oncologychronic lymphocytic leukemiaCD52humanized IgG1IVFerrajoli et al., 2001
Ibritumomab tiuxetanZevalinBiogen/Idec2002oncologyNon-Hodgkin’s lymphomaCD20murine IgG1 conjugated with Yttrium 90IVKrasner and Joyce, 2001
OmalizumabXolairGenentech/Novartis2003respiratoryasthmaIgEhumanized IgG1SCDavis, 2004
EfalizumabRaptivaGenentech2003AIIDpsoriasisCD11Ahumanized IgG1SCGauvreau et al., 2003
TositumomabBexxarGSK2003oncologyNon-Hodgkin’s lymphomaCD20murine IgG2a conjugated with iodine-131IVDavies, 2004
AdalimumabHumiraAbbott2003AIIDrheumatoid arthritisTNF alphahuman IgG1SCWeinblatt et al., 2003
CetuximabErbituxImClone/BMS2003oncologycolorectal cancerEGFRchimeric IgG1IVKies and Harari, 2002
I-131 ch-TNTShanghai Medipharm Biotech Co.2003oncologyadvanced lung cancerintracellular DNA in tumorschimeric IgG1 conjugated with iodine-131IVChen et al., 2005
BevacizumabAvastinGenentech2004oncologycolorectal and non-small cell lung cancerVEGFhumanized IgG1IVKerr, 2004
NatalizumabTysabriBiogen IDEC/Elan2004CNS/AIIDmultiple sclerosisVLA4humanized IgG1IVRudick and Sandrock, 2004
TocilizumabActemraRoche/Chugai2005AIIDCastleman's diseaseIL-6Rhumanized IgG1IVPaul-Pletzer, 2006
RanibizumabLucentisGenentech/Novartis2006ophthalmologywet age-related macular degenerationVEGFhumanized mab fragment of Avastininjection into the eyeKenneth and Kertes, 2006
PanitumumabVectibixAmgen2006oncologycolorectal cancerEGFRhuman IgG2IVCohenuram and Saif, 2007
Certolizumab pegolCimziaUCB-Schwarz2007AIIDrheumatoid arthritisTNF alphaPEGylated fragmentSCRutgeerts et al., 2007
EculizumabSolirisAlexion2007hematologyPNH (chronic hemolysis)C5ahumanized IgG2/IgG4 hybridIVRother et al., 2007
OfatumumabArzerraGSK2009oncologychronic lymphocytic leukemiaCD20human IgG1IVKeating et al., 2010
GolimumabSimponiJohnson & Johnson2009AIIDrheumatoid arthritisTNF alphahuman IgG1SCPappas et al., 2009
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