Therapeutic Antibodies PDF
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Therapeutic Therapeutic Antibodies Antibodies Editors Yuti Chernajovsky Ahuva Nissim Editors Yuti Chernajovsky Ahuva Nissim (cid:0)(cid:2) (cid:3)(cid:4) Handbook of Experimental Pharmacology Volume 181 Editor-in-Chief K.Starke,Freiburgi.Br. EditorialBoard S.Duckles,Irvine,CA M.Eichelbaum,Stuttgart D.Ganten,Berlin F.Hofmann,München C.Page,London W.Rosenthal,Berlin G.Rubanyi,SanDiego,CA Yuti Chernajovsky • Ahuva Nissim Editors Therapeutic Antibodies Contributors L. Chatenoud, Y. Chernajovsky, A.L. Epstein, Z. Eshhar, F. Goldblatt, I.S. Grewal, A. Honegger, P. Hu, D. Isenberg, A. Jakobovits, P. Jin, L.A. Khawli, T. Kishimoto, M. Kraft, S. Lien, A.S.-Y. Lo, N. Lonberg, H. Lowman, C.M. Lynch, D.C. Maneval, W.A. Marasco, N. Nishimoto, A. Nissim, Z. Pirot, D.J. Shealy, M. Shepard, J. Singh, X.R. Song, S.Visvanathan,Q.Zhu YutiChernajovsky AhuvaNissim ARCChairofRheumatology,CentreLead Bone&JointResearchUnit Bone&JointResearchUnit QueenMary’sSchoolofMedicine&Dentistry QueenMary’sSchoolofMedicine&Dentistry JohnVaneScienceCentre JohnVaneScienceCentre CharterhouseSquare CharterhouseSquare London,EC1M6BQ,UnitedKingdom London,EC1M6BQ,UnitedKingdom [email protected] [email protected] ISBN978-3-540-73258-7 e-ISBN978-3-540-73259-4 HandbookofExperimentalPharmacologyISSN0171-2004 LibraryofCongressControlNumber:2007931735 (cid:1)c Springer-VerlagBerlinHeidelberg2008 Thisworkissubjecttocopyright. 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CoverDesign:WMXDesignGmbH,Heidelberg Printedonacid-freepaper 987654321 springer.com Preface AntibodiesarenaturalinhibitorsofpathogensproducedbyBlymphocytes.Thein vivo biological process involving antigen presenting cells, T and B lymphocytes necessaryfortheirproductionarenotaddressedinthis book,butcanbe foundon anyimmunologytextbook. ThebreakthroughstudybyKohlerandMilsteinwastheabilitytoproduceinvitro antibodiesbycellfusion.Thisfindingcatapultedtheuseofantibodiesastherapeu- ticagents.WiththeemergenceofrecombinantDNAtechnologyandtheinnovative ingenuityof scientists, these magic bullets are now continuouslybeing developed bothforresearchandtherapeuticpurposesbyamyriadoftechniquesandtheiruse inmanyclinicalconditionsareatestimonyoftheirimportance.Thisbookprovides examplesof these developmentsand the currentareas of further research and im- provements. Wehaveinthisbookthecontributionofscientiststhathavebeeninvolvedinthe developmentof these therapeutic antibodiesfrom their conceptionand preclinical testing to their use in the clinic. We believe that each chapter contributes to our understandingofthisprocess.Innocasethepathfromdiscoverytoapplicationwas simpleandisthroughperseveranceandfurtherimprovementsthateachtherapeutic moietyreacheditsfinalmarketedform. Engineeringofantibodiestakesplaceallowingtheiruseastargetingdevicesof bothotherimmunomodulatorssuch ascytokinesorcellsthemselvesby theuse of chimeric receptors. The combination with gene transfer technologies to express some of these moieties directly by the cells of the patient and thus achieve long- termdeliveryisalso beinginvestigated.Asalwaysthereisroomforimprovement inthisfieldandweexpectthatintheyearstocomemoreofthesebiologicalswill becomeavailableinmorediversetherapeuticfields.Betterunderstandingofmolec- ularmechanismsandthefunctionoftargetedmoleculeswillleadtotheproduction ofmorespecifictargetedagents. The science ofpharmacologyhasbeenredrawnwith the entranceof these bio- logicalagentsin clinical practice. We need to consider introducingthe term “bio- pharmacology”when dealing with naturally occurring compoundsthat have been modifiedbyrecombinantDNA technology.Itisespeciallyrelevantincaseswhere v vi Preface twoormoredifferenttargetsarefoundinthesamemoleculesuchasinbi-specific antibodiesorimmunocytokines.Weareactuallywitnessingarevolutioninmedicine andthisbooksummarisesitverywell. WededicatethisbooktoKohlerandMilsteinfortheirseminalworkonantibody production. WethankProfessorGustavBornwhogaveustheopportunitytoeditthisbook; Nathan Fox and Lin Wells for secretarial assistance, all the authors and Susanne Dathe from Springer Verlag for their commitment and help to bring this book to light. London,UnitedKingdom AhuvaNissim London,UnitedKingdom YutiChernajovsky Contents Contributors ................................................... ix PartI Introduction HistoricalDevelopmentofMonoclonalAntibodyTherapeutics ......... 3 A.NissimandY.Chernajovsky PreclinicalSafetyEvaluationofMonoclonalAntibodies ............... 19 C.M.LynchandI.S.Grewal PartII MolecularDevelopmentsinAntibodyProduction EngineeringAntibodiesforStabilityandEfficientFolding ............. 47 A.Honegger HumanMonoclonalAntibodiesfromTransgenicMice ................ 69 N.Lonberg PartIII AntibodiestoCytokines Anti-TNFAntibodies:LessonsfromthePast,RoadmapfortheFuture... 101 D.J.ShealyandS.Visvanathan TherapeuticAnti-VEGFAntibodies................................ 131 S.LienandH.B.Lowman HumanizedAntihumanIL-6ReceptorAntibody,Tocilizumab.......... 151 N.NishimotoandT.Kishimoto vii viii Contents PartIV AntibodiestoCellMarkers Anti-CD20MonoclonalAntibodyinRheumatoidArthritisandSystemic LupusErythematosus............................................ 163 F.GoldblattandD.A.Isenberg Herceptin ...................................................... 183 H.M.Shepard,P.Jin,D.J.Slamon,Z.Pirot,andD.C.Maneval TheUseofCD3-SpecificAntibodiesinAutoimmuneDiabetes:AStep TowardtheInductionofImmuneToleranceintheClinic .............. 221 L.Chatenoud MonoclonalAntibodyTherapyforProstateCancer................... 237 A.Jakobovits Anti-IgEandOtherAntibodyTargetsinAsthma..................... 257 J.SinghandM.Kraft PartV DevelopmentofAntibody-BasedCellularandMolecularTherapies Cytokine,Chemokine, andCo-StimulatoryFusionProteinsforthe ImmunotherapyofSolidTumors .................................. 291 L.A.Khawli,P.Hu,andA.L.Epstein TheT-BodyApproach:RedirectingTCellswithAntibodySpecificity.... 329 Z.Eshhar IntracellularAntibodies(Intrabodies)andTheirTherapeuticPotential .. 343 A.S.-Y.Lo,Q.Zhu,andW.A.Marasco Index .............................................................375 Contributors L.Chatenoud Universite´ Rene´ Descartes, Paris, France,InstitutNationalde la Sante´ et de la RechercheMe´dicale,Unite´ 580,Paris,France,[email protected] Y.Chernajovsky BoneandJointResearchUnit,WilliamHarveyResearchInstitute,BartsandThe London,QueenMary’sSchoolofMedicineandDentistry,UniversityofLondon, CharterhouseSquare,LondonEC1M6BQ,UK A.L.Epstein DepartmentofPathology,KeckSchoolofMedicineattheUniversityofSouthern California,LosAngeles,CA,USA Z.Eshhar Departmentof Immunology,The WeizmannInstitute ofScience,P.O. Box 26, Rehovot76100,Israel,[email protected] F.Goldblatt CentreforRheumatology,DepartmentofMedicine,UniversityCollegeLondon Hospital, 3rd Floor Central, 250 Euston Road, London NW1 2PQ, UK, [email protected] I.S.Grewal DepartmentofPreclinicalTherapeutics,Seattle Genetics, Bothell, WA 98021, USA,[email protected] A.Honegger BiochemischesInstitut, Universita¨tZu¨rich,Winterthurerstrasse190,CH-8057 Zu¨rich,Switzerland,[email protected] P.Hu DepartmentofPathology,KeckSchoolofMedicineattheUniversityofSouthern California,LosAngeles,CA,USA ix x Contributors D.A.Isenberg CentreforRheumatology,DepartmentofMedicine,UniversityCollegeLondon Hospital,3rdFloorCentral,250EustonRoad,LondonNW12PQ,UK A.Jakobovits Agensys, Inc., 1545 17th Street, Santa Monica, CA 90404, USA, [email protected] P.Jin ReceptorBioLogix,Inc.,3350W.BayshoreRd.,Suite150,PaloAlto,CA94303, USA L.A.Khawli DepartmentofPathology,KeckSchoolofMedicineattheUniversityofSouthern California,LosAngeles,CA,USA Genentech, Inc., One DNA Way, South San Francisco, CA 94080, USA, [email protected] T.Kishimoto LaboratoryofImmuneRegulation,GraduateSchoolofFrontierBiosciences,Osaka University,1–3Yamadaoka,SuitaCity,Osaka565-0871,Japan M.Kraft Duke Asthma, Allergy and Airway Center Duke University Medical Center, Durham,NC27710,USA S.Lien Antibody Engineering,Protein Engineering, and ImmunologyDepartments, Genentech,Inc.,1DNAWay,SouthSanFrancisco,CA94080,USA A.S.-Y.Lo Dana-FarberCancerInstitute,HarvardMedicalSchool,44BinneyStreet,Boston MA02115,USA N.Lonberg Medarex, 521 Cottonwood Drive, Milpitas, CA 95035, USA, [email protected] H.B.Lowman Antibody Engineering,Protein Engineering, and ImmunologyDepartments, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA, [email protected] C.M.Lynch DepartmentofPreclinicalTherapeutics,SeattleGenetics,Bothell,WA98021,USA D.C.Maneval ReceptorBioLogix,Inc.,3350W.BayshoreRd.,Suite150,PaloAlto,CA94303, USA
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