Table Of ContentErnst 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
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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])
