Immunotherapy in 2020: Visions and Trends for Targeting Inflammatory Disease PDF
Preview Immunotherapy in 2020: Visions and Trends for Targeting Inflammatory Disease
Ernst Schering Foundation Symposium Proceedings 2006-4 Immunotherapy in 2020 Ernst Schering Foundation Symposium Proceedings 2006-4 Immunotherapy in 2020 Visions and Trends for Targeting Inflammatory Disease A. Radbruch, H.-D. Volk, K. Asadullah, W.-D. Doecke Editors With 10 Figures 123 SeriesEditors:G.StockandM.Lessl LibraryofCongressControlNumber:2007928116 ISSN 0947-6075 ISBN 978-3-540-70850-6 SpringerBerlinHeidelbergNewYork This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations,recitation,broadcasting,reproductiononmicrofilmsorinanyotherway,and storageindatabanks.Duplicationofthispublicationorpartsthereofispermittedonly undertheprovisionsoftheGermanCopyrightLawofSeptember9,1965,initscurrent version,andpermissionforusemustalwaysbeobtainedfromSpringer-Verlag.Violations areliableforprosecutionundertheGermanCopyrightLaw. SpringerisapartofSpringerScience+BusinessMedia springer.com ©Springer-VerlagBerlinHeidelberg2007 Theuseofgeneraldescriptivenames,registerednames,trademarks,etc.inthispublication doesnotemply,evenintheabsenceofaspecificstatemant,thatsuchnamesareexempt fromtherelevantprotectivelawsandregulationsandthereforfreeforgeneraluse.Product liability:Thepublishercannotguaranteetheaccuracyanyinformationaboutdosageand applicationcontainedinthisbook.Ineveryinduvidualcasetheusermustchecksuch informationbyconsultingtherelevantliterature. Editor:Dr.UteHeilmann,Heidelberg DeskEditor:WilmaMcHugh,Heidelberg ProductionEditor:MartinWeißgerber,Leipzig Coverdesign:design&production,Heidelberg Typesettingandproduction:LE-TEXJelonek,Schmidt&VöcklerGbR,Leipzig 21/3180/YL–543210 Printedonacid-freepaper Preface From22to24October2006,internationally renownedscientists from theEuropeanUnionandtheUnitedStatesmetinPotsdamnearBerlin, Germany, to discuss the future of chronic inflammatory disease treat- ment.Thetitleofthesymposium,organizedbytheErnstScheringFoun- dation,was“Immunotherapyin2020—VisionsandTrendsforTargeting InflammatoryDiseases”. The presentations covered the main mechanisms of immunoregula- tionsuchasperipheralandcentraltolerance,epigeneticprogramming, immunologicmemory,andregulatorynetworksininflammationaswell as novel experimental and clinical approaches for targeting inflamma- tioninautoimmunityandtransplantation.Groupdiscussionsfocusedon thequestionofhowrecentfindingsinimmunologicalresearchcanlead toimproveddiagnostics,newdrugs,andbettertherapies.Inthisregard, beside novel approaches, the individualization of immunomodulatory therapiesandtheestablishmentofreliablebiomarkersforassessingthe specificimmunesituationalongwithpatientresponsetotherapieswere discussed. In this volume, the symposium speakers give their view on current topicsofimmunopathophysiologyandimmunotherapy. The chapter by Prof. Rikard Holmdahl (Section for Inflammation Research, Lund University, Sweden) deals with the genetic basis of VI Preface inflammatory diseases by means of gene polymorphisms and its im- plications for the finding of new therapies. He describes how, based ontheprovengeneticcomponentofrheumatoidarthritisdemonstrated by clinical studies, a search for susceptibility genes in mice mod- els was performed, which led to the definition of novel pathways in- volvedintheimmunopathologyofarthritis.Concludingfromthis,novel therapeutic approaches are proposed which are experimentally proven yet. Theposttranscriptionalnetworksininflammationarethefocusofthe contributionfromDr.DimitrisKontoyiannisandcolleagues(Biomedical SciencesResearchCenter,Athens,Greece).Thebiosynthesisofinflam- matory mediators relies on the biogenesis as well as the utilization of theircorrespondingmRNAs.Theselatter“utilizationsteps”encompass posttranscriptional mechanisms that impose a series of flexible rate- limitingcontrolstomodifytheabundanceofamRNAaswellasitsrate oftranslationtoproteins.ThechapterdealswithRNA-bindingproteins that,forexample,bybindingtotheAU-richfamilyofelements,strin- gentlycontrolthematuration,localization, turnover,andtranslationof mRNAsfrominflammatorygenes. Prof. Andreas Radbruch and colleagues (German Rheumatism Re- search Center, Berlin, Germany) give an up-to-date overview on im- munologicalmemory,itsroleinchronicinflammation,anditsdramatic impact on the limitations of current immunotherapies. Concerning the latter, thehumoralmemory—which isprovidedbylong-livingplasma cells—isdiscussedinparticular.Theimmunologicmemoryisnotsuf- ficiently targeted by current immunotherapies that suppress ongoing immune activation. This is probably one of the main reasons frustrat- ingthecureofdiseasesbytherapies,exceptbonemarrowtransplanta- tion.Therefore,targetingoftheimmunologicmemory,whichprovides a consistent trigger of relapse, might be a major challenge for future immunotherapies. Adoptive T cell therapies are used to substitute the non-sufficient immune response of the recipient, e.g., to virus infection or malig- nancy. The use of unselective allogeneic T cell therapies (e.g., donor lymphocyte infusion), however, is limited by major clinical complica- Preface VII tionssuchasgraft-versus-hostdisease.Dr.StephenGottschalkandcol- leagues(CenterforCellandGeneTherapy,BaylorCollegeofMedicine, Houston,Texas,USA)dealwiththedevelopmentofautologousantigen- specificTcelltherapiesforthetreatmentofdifferentEpstein-Barrvirus- associatedmalignancies.Ifeffective,thesestrategiesmighthavebroad implicationsalsoforotherindications,e.g.,humantumorswithdefined antigens. Interesting novel perspectives of a rather old approach, polyclonal antibodytherapy,aregiveninthecontributionbyDrs.RolandBuelow andWimvanSchooten(TherapeuticHumanPolyclonalsInc.,Mountain View,California,USA).Despitetheirstrongdevelopmentinthelastfew years(e.g.,humanization, novelantibodyderivatives,andconjugates), monoclonalantibodytherapieshaveprincipallimitations. Hence,their effectiveness especially in devastating diseases such as cancer and in- fectionsisoftenlimitedbythecapacityofsinglemonoclonalantibodies totriggerimmuneeffectorfunctionsaswellasbytheadaptivityofthe affectedcellsandthepathogens(e.g.,mutationorlossofantigenexpres- sion).Theselimitationsofmono-specificantibodiesmightbeovercome bytherapeuticoligoclonal(mixturesofmonoclonals)andpolyclonalan- tibodypreparations.Amajorstepforwardforthelatteristhegeneration ofhumanpolyclonalantiseraintransgenicanimals. The chapter by Prof. Hans-Dieter Volk and colleagues (Institute of Medical Immunology, Charite´ Hospital, Berlin, Germany) deals with a major challenge for all immunomodulatory interventions, the indi- vidualizationofimmunotherapy.Bymeansofimmunosuppressiveand anti-infective therapy in transplant patients and patients with autoim- mune disease, the authors describe how the patients can be selected for special adjuvant therapies, how the most suitable immunosuppres- sion is selected for the single patient, and how the effect of a specific immunomodulatorytherapycanbemonitoredtoallowitstimelyadjust- menttobesufficientwhileminimizingthesideeffects. Allinall,themeetingwascharacterizedbyveryintensiveandfruitful discussions involving the concepts and thinking of researchers from academia, pharmaceutical industry and clinics. There was agreement that only through the close cooperation of everyone involved in this VIII Preface researchfieldabetterunderstandingandfinallyabetterimmunotherapy forautoimmunediseasesandallotransplantationcanbeachieved. WewouldliketothanktheErnstScheringFoundationforsponsoring this meeting as well as all speakers and participants for their valuable input. AndreasRadbruch Hans-DieterVolk KhusruAsadullah Wolf-DietrichDoecke Contents Nature’sChoiceofGenesControllingChronicInflammation R.Holmdahl . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 TargetingofMemory U.Niesner,I.Albrecht,A.Radbruch . . . . . . . . . . . . . . . 17 Post-transcriptionalRegulatorsinInflammation: ExploringNewAvenuesinBiologicalTherapeutics V.Katsanou,M.Dimitriou,D.L.Kontoyiannis . . . . . . . . . . 37 ImmunomodulatoryTherapies: ChallengesofIndividualizedTherapyStrategies H.D.Volk,B.Sawitzki,F.Kern,C.Ho¨flich,R.Sabat,P.Reinke . 59 TCellTherapies S.Gottschalk,C.M.Bollard,K.C.Straathof,C.U.Louis, B.Savoldo,G.Dotti,M.K.Brenner,H.E.Heslop,C.M.Rooney . 69 TheFutureofAntibodyTherapy R.Buelow,W.vanSchooten . . . . . . . . . . . . . . . . . . . . 83 ListofEditorsandContributors Editors Radbruch,A. DeutschesRheuma-ForschungszentrumBerlin, Schumanstr.21/22,10127Berlin,Germany (e-mail:[email protected]) Volk,H.-D. InstituteofMedicalImmunology,Charite´ CampusMitte, Schumannstr.20/21,10117Berlin,Germany (e-mail:hans-dieter.volk@charite) Asadullah,K. ScheringAG,Mu¨llerstr.178,13342Berlin,Germany (e-mail:[email protected]) Doecke,W.-D. ScheringAG,Mu¨llerstr.178,13342Berlin,Germany (e-mail:[email protected])
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