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METHODSINMOLECULARBIOLOGYSeriesEditorJohnM.
WalkerSchoolofLifeandMedicalSciencesUniversityofHertfordshireHatfield,Hertfordshire,AL109AB,UKForfurthervolumes:http://www.
springer.
com/series/7651HumanMonoclonalAntibodiesMethodsandProtocolsSecondEditionEditedbyMichaelSteinitzDepartmentofPathology,TheHebrewUniversity,HadassahMedicalSchool,Jerusalem,IsraelEditorMichaelSteinitzDepartmentofPathologyTheHebrewUniversityHadassahMedicalSchoolJerusalem,IsraelISSN1064-3745ISSN1940-6029(electronic)MethodsinMolecularBiologyISBN978-1-4939-8957-7ISBN978-1-4939-8958-4(eBook)https://doi.
org/10.
1007/978-1-4939-8958-4LibraryofCongressControlNumber:2018964050SpringerScience+BusinessMedia,LLC,partofSpringerNature2019Thisworkissubjecttocopyright.
AllrightsarereservedbythePublisher,whetherthewholeorpartofthematerialisconcerned,specicallytherightsoftranslation,reprinting,reuseofillustrations,recitation,broadcasting,reproductiononmicrolmsorinanyotherphysicalway,andtransmissionorinformationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilarmethodologynowknownorhereafterdeveloped.
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Thepublisher,theauthors,andtheeditorsaresafetoassumethattheadviceandinformationinthisbookarebelievedtobetrueandaccurateatthedateofpublication.
Neitherthepublishernortheauthorsortheeditorsgiveawarranty,expressorimplied,withrespecttothematerialcontainedhereinorforanyerrorsoromissionsthatmayhavebeenmade.
Thepublisherremainsneutralwithregardtojurisdictionalclaimsinpublishedmapsandinstitutionalafliations.
ThisHumanaPressimprintispublishedbytheregisteredcompanySpringerScience+BusinessMedia,LLC,partofSpringerNature.
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S.
A.
DedicationThisbookisdedicatedtoGeorgeKlein,1925–2016,agiantcreativeandstimulatingscientistofinniteknowledge,friend,andmentor.
Hislegacyisanever-fadinglighthousetohundredsofformerstudents,co-workers,colleagues,andfriends.
vPrefaceAsecondeditionofSpringerProtocolsbookHumanMonoclonalAntibodiesisanaturaloutcomeoftherapiddevelopmentsintheareaandtheremarkableinterestattractedbyour2014rsteditionofthebook.
Itisamazingwhatarapidanddramaticdevelopmenthasoccurredintheeldofhumanmonoclonalantibodiessincethersttimethesewereproducedinthelaboratory.
ItwasthepioneeringstudyinitiatedbyProfessorGeorgeKleininStockholmin1977[1]thatshowedthefeasibilityofmakingsuchantibodiesfromimmortalizedperipheralbloodantigen-committedhumanBlymphocytes.
Theextensivebasicimmuneresearchwhichhastakenplaceduringthelastyearsrapidlyconvergedintotheclinic.
TheFastanddramaticdevelopmentofnovelimmunetreatmentsintheclinicusinghumanmonoclonalantibodiesurgedtheimprovementsoftraditionalandalsocompletelynewtechniquesinvolvedintheproductionoftheantibodies.
Theintroduc-tionofmonoclonalantibodiesdirectedagainstlymphocytecell-surfacecostimulatory/immunecheckpointreceptorsthatmediatetheimmuneresponsehasbeenrevolutionary.
Theseantibodiesenableovercomeimmuneunresponsiveness(i.
e.
,tolerance)ofTcells.
Antibodiesagainstcostimulatorylymphocytereceptorswhichnowareusedintheclinicprovedverybenecialfortumorpatientsatleastinrelationtosometypesofcancer.
Continuousprogressinmoleculartechniquesenablesgenuinemanagementofantibodymolecules.
SuchreagentsintroducedintocytotoxicTcellspromisenewhorizonsforthetreatmentofcancerpatients.
ThepresentSpringerProtocolsbookreectssomeoftherecentdevelopmentsinthearea.
Itincludesseveralcompletelynewchaptersrelatedtotopicsthatwerenotdiscussedintherstedition.
Inaddition,somechaptersfromthersteditionareupdatedwithnecessaryrevisions.
Similartotherstedition,besidesthedetailedspecictechnicalprotocols,thereareafewreviewmanuscriptstoo.
Jerusalem,IsraelMichaelSteinitzReference1.
SteinitzM,KleinG,KoskimiesS,Ma¨kela¨O(1977)EBVvirusinducedBlymphocytecelllinesproducingspecicantibody.
Nature269:420–422viiContentsPrefaceviiContributors.
xi1HumanMonoclonalAntibodies:TheBenetsofHumanization1HermanWaldmann2CancerImmunotherapy:TheDawnofAntibodyCocktails.
11IlariaMarrocco,DonatellaRomaniello,andYosefYarden3IgMNaturalAutoantibodiesinPhysiologyandtheTreatmentofDisease.
53MahboobehFereidan-Esfahani,TarekNayfeh,ArthurWarrington,CharlesL.
Howe,andMosesRodriguez4MonoclonalAntibodiesfortheTreatmentofMelanoma:PresentandFutureStrategies83MadhuriBhandaruandAnandRotte5AnEfcientMethodtoGenerateMonoclonalAntibodiesfromHumanBCells109JennaJ.
Guthmiller,HaleyL.
Dugan,KarlynnE.
Neu,LindaYu-LingLan,andPatrickC.
Wilson6IsolationofAntigen-Specic,Antibody-SecretingCellsUsingaChip-BasedImmunospotArray147HiroyukiKishi,TatsuhikoOzawa,HiroshiHamana,EijiKobayashi,andAtsushiMuraguchi7PuricationofHumanMonoclonalAntibodiesandTheirFragments.
163NicoleUlmer,SebastianVogg,ThomasMu¨ller-Spa¨th,andMassimoMorbidelli8One-TubeMulticolorFlowCytometryAssay(OTMA)forComprehensiveImmunophenotypingofPeripheralBlood189Anna-JasminaDonaubauer,PaulF.
Ru¨hle,InaBecker,RainerFietkau,UdoS.
Gaipl,andBenjaminFrey9HumanizationandSimultaneousOptimizationofMonoclonalAntibody213TaichiKuramochi,TomoyukiIgawa,HiroyukiTsunoda,andKunihiroHattori10AntibodyFragmentsHumanization:BeginningwiththeEndinMind231NicolasAubreyandPhilippeBilliald11Antigen-SpecicHumanMonoclonalAntibodiesfromTransgenicMice253SusanaMagadanMompoandAfricaGonzalez-Fernandez12ReningtheQualityofMonoclonalAntibodies:GraftingUniquePeptide-BindingSiteintheFabFramework293JeremyD.
KingandJohnC.
Williams13BasicProceduresforDetectionandCytotoxicityofChimericAntigenReceptors299KeichiroMihara,TetsumiYoshida,andJoyeetaBhattacharyyaix14RapidChimerizationofAntibodies307KojiHashimoto,KoheiKurosawa,HidetakaSeo,andKunihiroOhta15PhageDisplayTechnologyforHumanMonoclonalAntibodies.
319MarcoDalFerro,SerenaRizzo,EmanuelaRizzo,FrancescaMarano,ImmacolataLuisi,OlgaTarasiuk,andDanieleSblattero16RecombinantAntibodySelectionsbyCombiningPhageandYeastDisplay339FortunatoFerrara,MariaFeliciaSoluri,andDanieleSblattero17EpitopeMappingviaPhageDisplayfromSingle-GeneLibraries353ViolaFu¨hner,PhilipAlexanderHeine,KilianJohannesCarlZilkens,DorisMeier,KristianDanielRalphRoth,GustavoMarcalSchmidtGarciaMoreira,MichaelHust,andGiulioRusso18AHigh-ThroughputMagneticNanoparticle-BasedSemi-AutomatedAntibodyPhageDisplayBiopanning377AngelaChiewWenCh'ng,AzimahAhmad,ZoltanKonthur,andTheamSoonLim19ABindingPotencyAssayforPritumumabandEcto-DomainVimentin.
401IvanBabic,SantoshKesari,andMarkC.
Glassy20AMethodtoDetecttheBindingofHyper-GlycosylatedFragmentCrystallizable(Fc)RegionofHumanIgG1toGlycanReceptors417PatriciaBlundellandRichardPleass21ACell-BasedReporterAssayMeasuringtheActivationofFcGammaReceptorsInducedbyTherapeuticMonoclonalAntibodies423MichihikoAoyama,MinoruTada,andAkikoIshii-Watabe22"BIClonals":ProductionofBispecicAntibodiesinIgGFormatinTransientlyTransfectedMammalianCells.
431DanaLitvak-Greenfeld,LilachVaks,StavDror,LimorNahary,andItaiBenhar23ProductionofStabilizedAntibodyFragmentsintheE.
coliBacterialCytoplasmandinTransientlyTransfectedMammalianCells455RacheliBirnboim-Perach,YehuditGrinberg,LilachVaks,LimorNahary,andItaiBenharIndex481xContentsContributorsAZIMAHAHMADInstituteforResearchinMolecularMedicine,UniversitiSainsMalaysia,Penang,MalaysiaMICHIHIKOAOYAMADivisionofBiologicalChemistryandBiologicals,NationalInstituteofHealthSciences,Kawasaki,Kanagawa,JapanNICOLASAUBREYUMRUniversite-INRAISP1282,BioMAP,UniversitedeTours,Tours,FranceIVANBABICDepartmentofTranslationalNeurosciencesandNeurotherapeutics,JohnWayneCancerInstitute,SantaMonica,CA,USAINABECKERDepartmentofRadiationOncology,Universita¨tsklinikumErlangen,Friedrich-Alexander-Universita¨tErlangen-Nu¨rnberg,Erlangen,GermanyITAIBENHARSchoolofMolecularCellBiologyandBiotechnology,TheGeorgeS.
WiseFacultyofLifeSciences,Tel-AvivUniversity,RamatAviv,IsraelMADHURIBHANDARUDepartmentofDermatologyandSkinScience,UniversityofBritishColumbia,Vancouver,BC,CanadaJOYEETABHATTACHARYYADepartmentofCardiacResearch,CumballaHillHospitalandHeartInstitute,Mumbai,IndiaPHILIPPEBILLIALDSchoolofPharmacy,Paris-SudUniversity,Chatenay-Malabry,FranceRACHELIBIRNBOIM-PERACHSchoolofMolecularCellBiologyandBiotechnology,TheGeorgeS.
WiseFacultyofLifeSciences,Tel-AvivUniversity,RamatAviv,IsraelPATRICIABLUNDELLLiverpoolSchoolofTropicalMedicine,Liverpool,UKANGELACHIEWWENCH'NGInstituteforResearchinMolecularMedicine,UniversitiSainsMalaysia,Penang,MalaysiaMARCODALFERRODepartmentofLifeSciences,UniversityofTrieste,Trieste,ItalyANNA-JASMINADONAUBAUERDepartmentofRadiationOncology,Universita¨tsklinikumErlangen,Friedrich-Alexander-Universita¨tErlangen-Nu¨rnberg,Erlangen,GermanySTAVDRORSchoolofMolecularCellBiologyandBiotechnology,TheGeorgeS.
WiseFacultyofLifeSciences,Tel-AvivUniversity,RamatAviv,IsraelHALEYL.
DUGANCommitteeonImmunology,UniversityofChicago,Chicago,IL,USAMAHBOOBEHFEREIDAN-ESFAHANIDepartmentofNeurology,MayoClinic,Rochester,MN,USAFORTUNATOFERRARASpecicaInc.
,SantaFe,NM,USARAINERFIETKAUDepartmentofRadiationOncology,Universita¨tsklinikumErlangen,Friedrich-Alexander-Universita¨tErlangen-Nu¨rnberg,Erlangen,GermanyBENJAMINFREYDepartmentofRadiationOncology,Universita¨tsklinikumErlangen,Friedrich-Alexander-Universita¨tErlangen-Nu¨rnberg,Erlangen,GermanyVIOLAFU¨HNERAbteilungBiotechnologie,Institutfu¨rBiochemie,BiotechnologieundBioinformatik,TechnischeUniversita¨tBraunschweig,Braunschweig,GermanyUDOS.
GAIPLDepartmentofRadiationOncology,Universita¨tsklinikumErlangen,Friedrich-Alexander-Universita¨tErlangen-Nu¨rnberg,Erlangen,GermanyMARKC.
GLASSYDepartmentofTranslationalNeurosciencesandNeurotherapeutics,JohnWayneCancerInstitute,SantaMonica,CA,USA;TranslationalNeuro-OncologyLaboratory,UCSDMooresCancerCenter,LaJolla,CA,USA;NascentBiotech,Inc.
,SanDiego,CA,USAxiAFRICAGONZALEZ-FERNANDEZImmunology,CentrodeInvestigacionesBiomedicas(CINBIO),CentrodeInvestigacionSingulardeGalicia,InstitutodeInvestigacionSanitariaGaliciaSur,UniversidaddeVigo,Vigo,SpainYEHUDITGRINBERGSchoolofMolecularCellBiologyandBiotechnology,TheGeorgeS.
WiseFacultyofLifeSciences,Tel-AvivUniversity,RamatAviv,IsraelJENNAJ.
GUTHMILLERDepartmentofMedicine,SectionofRheumatology,TheKnappCenterforLupusandImmunology,UniversityofChicago,Chicago,IL,USAHIROSHIHAMANADepartmentofImmunology,GraduateSchoolofMedicineandPharmaceuticalSciences,UniversityofToyama,Toyama,JapanKOJIHASHIMOTODepartmentofLifeSciences,GraduateSchoolofArtsandSciences,TheUniversityofTokyo,Tokyo,JapanKUNIHIROHATTORIResearchDivision,ChugaiPharmaceutical,Kamakura,Kanagawa,JapanPHILIPALEXANDERHEINEAbteilungBiotechnologie,Institutfu¨rBiochemie,BiotechnologieundBioinformatik,TechnischeUniversita¨tBraunschweig,Braunschweig,GermanyCHARLESL.
HOWEDepartmentofNeurology,MayoClinic,Rochester,MN,USAMICHAELHUSTAbteilungBiotechnologie,Institutfu¨rBiochemie,BiotechnologieundBioinformatik,TechnischeUniversita¨tBraunschweig,Braunschweig,GermanyTOMOYUKIIGAWAChugaiPharmabodyResearchPte.
Ltd.
,Singapore,SingaporeAKIKOISHII-WATABEDivisionofBiologicalChemistryandBiologicals,NationalInstituteofHealthSciences,Kawasaki,Kanagawa,JapanSANTOSHKESARIDepartmentofTranslationalNeurosciencesandNeurotherapeutics,JohnWayneCancerInstitute,SantaMonica,CA,USAJEREMYD.
KINGDepartmentofMolecularMedicine,BeckmanResearchInstituteatCityofHope,Duarte,CA,USAHIROYUKIKISHIDepartmentofImmunology,GraduateSchoolofMedicineandPharmaceuticalSciences,UniversityofToyama,Toyama,JapanEIJIKOBAYASHIDepartmentofImmunology,GraduateSchoolofMedicineandPharmaceuticalSciences,UniversityofToyama,Toyama,JapanZOLTANKONTHURDepartmentofBiomolecularSystems,MaxPlanckInstituteofColloidsandInterfaces,Potsdam,GermanyTAICHIKURAMOCHIChugaiPharmabodyResearchPte.
Ltd.
,Singapore,SingaporeKOHEIKUROSAWADepartmentofLifeSciences,GraduateSchoolofArtsandSciences,TheUniversityofTokyo,Tokyo,JapanLINDAYU-LINGLANCommitteeonImmunology,UniversityofChicago,Chicago,IL,USATHEAMSOONLIMInstituteforResearchinMolecularMedicine,UniversitiSainsMalaysia,Penang,Malaysia;AnalyticalBiochemistryResearchCentre,UniversitiSainsMalaysia,Penang,MalaysiaDANALITVAK-GREENFELDSchoolofMolecularCellBiologyandBiotechnology,TheGeorgeS.
WiseFacultyofLifeSciences,Tel-AvivUniversity,RamatAviv,IsraelIMMACOLATALUISIDepartmentofLifeSciences,UniversityofTrieste,Trieste,ItalySUSANAMAGADANMOMPOImmunology,CentrodeInvestigacionesBiomedicas(CINBIO),CentrodeInvestigacionSingulardeGalicia,InstitutodeInvestigacionSanitariaGaliciaSur,UniversidaddeVigo,Vigo,SpainFRANCESCAMARANODepartmentofLifeSciences,UniversityofTrieste,Trieste,ItalyILARIAMARROCCODepartmentofBiologicalRegulation,WeizmannInstituteofScience,Rehovot,IsraelxiiContributorsDORISMEIERAbteilungBiotechnologie,Institutfu¨rBiochemie,BiotechnologieundBioinformatik,TechnischeUniversita¨tBraunschweig,Braunschweig,GermanyKEICHIROMIHARADepartmentofHematologyandOncology,ResearchInstituteforRadiationBiologyandMedicine,HiroshimaUniversity,Hiroshima,JapanMASSIMOMORBIDELLIETHZurich,InstituteforChemicalandBioengineering,Zurich,SwitzerlandGUSTAVOMARCALSCHMIDTGARCIAMOREIRAAbteilungBiotechnologie,Institutfu¨rBiochemie,BiotechnologieundBioinformatik,TechnischeUniversita¨tBraunschweig,Braunschweig,GermanyTHOMASMU¨LLER-SPA¨THETHZurich,InstituteforChemicalandBioengineering,Zurich,SwitzerlandATSUSHIMURAGUCHIDepartmentofImmunology,GraduateSchoolofMedicineandPharmaceuticalSciences,UniversityofToyama,Toyama,JapanLIMORNAHARYSchoolofMolecularCellBiologyandBiotechnology,TheGeorgeS.
WiseFacultyofLifeSciences,Tel-AvivUniversity,RamatAviv,IsraelTAREKNAYFEHDepartmentofNeurology,MayoClinic,Rochester,MN,USAKARLYNNE.
NEUDepartmentofMedicine,SectionofRheumatology,TheKnappCenterforLupusandImmunology,UniversityofChicago,Chicago,IL,USA;CommitteeonImmunology,UniversityofChicago,Chicago,IL,USAKUNIHIROOHTADepartmentofLifeSciences,GraduateSchoolofArtsandSciences,TheUniversityofTokyo,Tokyo,JapanTATSUHIKOOZAWADepartmentofImmunology,GraduateSchoolofMedicineandPharmaceuticalSciences,UniversityofToyama,Toyama,JapanRICHARDPLEASSLiverpoolSchoolofTropicalMedicine,Liverpool,UKSERENARIZZODepartmentofLifeSciences,UniversityofTrieste,Trieste,ItalyEMANUELARIZZODepartmentofLifeSciences,UniversityofTrieste,Trieste,ItalyMOSESRODRIGUEZDepartmentofNeurology,MayoClinic,Rochester,MN,USADONATELLAROMANIELLODepartmentofBiologicalRegulation,WeizmannInstituteofScience,Rehovot,IsraelKRISTIANDANIELRALPHROTHAbteilungBiotechnologie,Institutfu¨rBiochemie,BiotechnologieundBioinformatik,TechnischeUniversita¨tBraunschweig,Braunschweig,GermanyANANDROTTEDepartmentofClinicalPharmacology,GenentechResearchandEarlyDevelopment,SouthSanFrancisco,CA,USA;DepartmentofClinicalandRegulatoryAffairs,NevroCorp.
,RedwoodCity,CA,USAPAULF.
RU¨HLEDepartmentofRadiationOncology,Universita¨tsklinikumErlangen,Friedrich-Alexander-Universita¨tErlangen-Nu¨rnberg,Erlangen,GermanyGIULIORUSSOAbteilungBiotechnologie,Institutfu¨rBiochemie,BiotechnologieundBioinformatik,TechnischeUniversita¨tBraunschweig,Braunschweig,GermanyDANIELESBLATTERODepartmentofLifeSciences,UniversityofTrieste,Trieste,ItalyHIDETAKASEODepartmentofLifeSciences,GraduateSchoolofArtsandSciences,TheUniversityofTokyo,Tokyo,JapanMARIAFELICIASOLURIDepartmentofHealthSciencesandIRCAD,UniversityofPiemonteOrientale(UPO),Novara,ItalyMINORUTADADivisionofBiologicalChemistryandBiologicals,NationalInstituteofHealthSciences,Kawasaki,Kanagawa,JapanOLGATARASIUKDepartmentofHealthSciencesandIRCAD,UniversityofEasternPiedmont,Novara,ItalyContributorsxiiiHIROYUKITSUNODAResearchDivision,ChugaiPharmaceutical,Kamakura,Kanagawa,JapanNICOLEULMERETHZurich,InstituteforChemicalandBioengineering,Zurich,SwitzerlandLILACHVAKSSchoolofMolecularCellBiologyandBiotechnology,TheGeorgeS.
WiseFacultyofLifeSciences,Tel-AvivUniversity,RamatAviv,IsraelSEBASTIANVOGGETHZurich,InstituteforChemicalandBioengineering,Zurich,SwitzerlandHERMANWALDMANNSirWilliamDunnSchoolofPathology,OxfordUniversity,Oxford,UKARTHURWARRINGTONDepartmentofNeurology,MayoClinic,Rochester,MN,USAJOHNC.
WILLIAMSDepartmentofMolecularMedicine,BeckmanResearchInstituteatCityofHope,Duarte,CA,USAPATRICKC.
WILSONDepartmentofMedicine,SectionofRheumatology,TheKnappCenterforLupusandImmunology,UniversityofChicago,Chicago,IL,USA;CommitteeonImmunology,UniversityofChicago,Chicago,IL,USAYOSEFYARDENDepartmentofBiologicalRegulation,WeizmannInstituteofScience,Rehovot,IsraelTETSUMIYOSHIDADepartmentofHematologyandOncology,ResearchInstituteforRadiationBiologyandMedicine,HiroshimaUniversity,Hiroshima,JapanKILIANJOHANNESCARLZILKENSYUMABGmbH,Braunschweig,GermanyxivContributors