Gene Therapy of Cancer PDF
Preview Gene Therapy of Cancer
GENE THERAPY OF CANCER ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY Editorial Board: NATHAN BACK,State UniversityofNew YorkatBuffalo IRUN R. COHEN,The Weizmann InstituteofScience DAVID KRITCHEVSKY, WistarInstitute ABEL LAJTHA,N. S. KlineInstituteforPsychiatricResearch RODOLFO PAOLETTI,UniversityofMilan RecentVolumesinthisSeries Volume443 ADVANCES IN LACTOFERRIN RESEARCH EditedbyGenevieveSpik,DominiqueLegrand,Joel Mazurier,Annick Pierce, andJean-Paul Perraudin Volume444 REPRODUCTIVETOXICOLOGY: In Vitro GermCellDevelopmentalToxicology,from SciencetoSocialand IndustrialDemand EditedbyJesusdel Mazo Volume445 MATHEMATICALMODELING IN EXPERIMENTALNUTRITION EditedbyAndrewJ. CliffordandHans-Georg Muller Volume446 MOLECULARANDCELLULAR MECHANISMSOFNEURONAL PLASTICITY: Basicand Clinical Implications EditedbyYigal H. Ehrlich Volume447 L1POXYGENASES ANDTHEIRMETABOLITES: Biological Functions EditedbySantoshNigamandCecil R. Pace-Asciak Volume448 COPPERTRANSPORTANDITS DISORDERS: MolecularandCellularAspects EditedbyArturo LeoneandJulian F. B. Mercer Volume449 VASOPRESSIN ANDOXYTOCIN: Molecular,Cellular,andClinical Advances Editedby Hans H. Zingg,CharlesW. Bourque,andDanielG. Bichet Volume450 ADVANCES IN MODELINGANDCONTROLOF VENTILATION EditedbyRichard L. Hughson, DavidA. Cunningham,andJamesDuffin Volume451 GENETHERAPYOFCANCER Editedby PeterWalden,UweTrefzer, WolframSterry,and Farzin Farzaneh Volume452 MECHANISMSOFLYMPHOCYTEACTIVATION AND IMMUNE REGULATION VII: MolecularDeterminantsofMicrobial Immunity EditedbySudhirGupta,AlanSher,andRaft Ahmed AContinuationOrderPlanisavailableforthisseries.Acontinuationorderwillbringdeliveryofeachnewvolume immediatetyuponpublication.Volumesarebilledonlyuponactualshipment.Forfurtherinformationpleasecontact thepublisher. GENE THERAPY OF CANCER Edited by Peter Walden Uwe Trefzer Wo lfram Sterry Humboldt University Berlin, Gennany and F arzin F arzaneh King's College School of Medicine and Dentistry London, United Kingdom Assistant Editor Patricia Zambon Humboldt University Berlin, Gennany SPRINGER SCIENCE+BUSINESS MEDIA, LLC Library of Congress Cataloging in Publication Data Gene therapy of cancer f edited by Peter Walden ... [et al.); assistant editor, Patricia Zambon. p. cm.-(Advances in experimental medicineand biology; v. 451) "Proceedings of the Third European Conference on Gene Therapy of Cancer, held September 11-13, 1997, in Berlin, Germany"-Tp. verso. Includes bibliographical references and indexes. ISBN 978-1-4613-7444-2 ISBN 978-1-4615-5357-1 (eBook) DOI 10.1007/978-1-4615-5357-1 1. Cancer-Gene therapy-Congresses. l. Walden, Peter. II. European Conference on Gene Therapy of Cancer (3rd: 1997: Berlin, Germany) III. Series. [DNLM: 1. Neoplasms-therapy congresses. 2. Gene Therapy-methods congresses. 3. Neo plasms-immunology congresses. 4. Gene Targeting congresses. 5. Clinical Trials congresses. WIAD559 vA51 1998) RC271.G45G4642 1998 616.99'40426-dc21 DNLM/DLC 98-39294 for Library of Congress CIP Proceedings of the Third European Conference on Gene Therapy of Cancer, held September II - 13, 1997, in Berlin, Germany © 1998 Springer Science+Business Media New York Originally published by Plenum Press, New York in 1998 Softcover reprint ofthe hardcover 1s t edition 1998 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher PREFACE Initially introduced as a therapeutic strategy for disorders caused by inherited gene defects such as Gaucher's disease (adenosine deaminase deficiency) or adrenoleuk odystrophy, gene therapy has been considered for and applied to a variety ofother dis eases includingviral infectionslike AIDS,and, mostextensively,cancer. More than 2100 patients world-wide have been enrolled ingene therapy trials since the first clinical study in 1990. The majority of these trials deal with cancer (60% of the current 71 trials in Europe). The efforts in cancer gene therapy focus on three types ofapproaches: chemo gene therapy, i. e. the introduction ofgenes that confer susceptibility to chemotherapeu tics; immunogene therapy, which involves modulation ofthe patient's immune response capacity; tumour suppressor gene-mediated inhibition of tumour growth promotors like oncogenes and cytokines; and inhibitors oftumour angiogenesis and invasiveness. The successful clinical applicationofeach ofthesecancergenetherapyapproaches isdepend enton the developmentofefficientgenetargetinganddeliverysystems. Cancer is one ofthe major health problems ofour time and we battle it with un precedented vigourand resources, utilizing the mostadvancedconcepts and techniques in modem medicine. Cancerresearch has been adriving force for many areas in biomedical as well as in basic biological sciences. Thus, cancer gene therapy has evolved alongside the recent rapid developments in molecular genetics, cell biology, and immunology, and exploits the major breakthroughs in the understanding ofthe molecular pathogenesis of these diseases. However, despite the considerable progress, advanced stage cancer is still incurable in mostcases. Anumberofgenetic alterationsare required for malignanttransformation leadingto growth disregulation and tumour development. However, cancer develops only ifthe al tered cells can evade the cellular, tissue-specific, and immune surveillance systems that control and ensure the body's integrity, and that usually eliminate aberrant cells. Tumour cells, as a consequence, are highly selected cells that not only share tissue-specific traits oftheir normal untransformed counterparts as well as tumour-associated properties but alsoreflectthe historyandthepresenceofthe body'santi-tumouractivities.Theresulting heterogeneity is often strengthened by a perpetuated genetic instability. In consequence, cancer is an extremely diverse group ofdiseases with fundamental tissue-specific differ ences and differences unique to each individual that thus complicate the development of coherenttreatmentstrategies. The clinical trials performed so far have yielded variable anti-tumour activities in cludingsome partialandsomecompleteresponses, with remarkablymildsideeffects. AI- v vi Preface though cure from the disease hasonly been achievedoccasionally, much practical experi enceand ahugebodyofinformationwasobtained. Thisprovidesasignificantlyimproved basis for future developments. The novel findings include many reports showingthat sui cide or tumour suppressor gene-based therapies can induce broad ranging responses, in cludingthe induction ofimmune-mediatedanti-tumoureffects. Currently,the most urgent goals are the better understanding ofthe mechanisms involved in these co-operative ef fects, their exploitation for new treatment strategies, and the design oftargetable vectors for efficient in vivo transfer and expression oftherapeutic genes. Advances in each of these areas will significantlyhelp the developmentofnew strategies for treatmentofcan cerand will bea majorsteptowards the goal ofimproved therapy andultimately the cure ofthe disease. The European Conference on Gene Therapy ofCancer series provides a forum for the discussion and evaluation ofthe most recent advances in moleculargenetics, cell biol ogy, immunology, clinical trials and the design of new concepts for cancer treatment. Bringingtogetherexpertsfrom differentfields facilitates orchestrationofthe forces in the battle against cancer. The 3rdEuropean Conference on Gene Therapy ofCancer was held from September 11 through 13, 1997 at the Charite, Medical Faculty ofthe Humboldt University in Berlin. This proceedings volume gives a comprehensive overview of the work presentedat theconference,andofthe currentstatus incancergene therapy. PeterWalden UweTrefzer Wolfram Sterry Farzin Farzaneh ACKNOWLEDGMENTS The German Federal Ministry for Education, Science, Research, and Technology was the main sponsorofthe 3rdEuropean Conferenceon Gene TherapyofCancer. Finan cial supportwasalso provided bythefollowing companies: • Bayer • Chiron • Essex Pharma • HoechstMarion Roussel • Rhone-Poulenc Rorer • Dr. Karl Thomae. Theeditorsare solelyresponsible forthecontentsofthis volume. vii CONTENTS TumorBiology I. ExpressionGeneticsinCancerResearch,Prognosis,andTherapy . K.1. Martinand R. Sager 2. PatternsofChromosomalImbalancesinCarcinomasoftheRespiratoryTract 9 IverPetersen,UlrikeBockmuhl,SimonePetersen,GunterWolf,and ManfredDietel 3. InhibitionofTumorigenesisinaMurineB-CellLymphomaTransplantModel byc-MycComplementaryOligonucleotides 17 JanetB. SmithandEricWickstrom 4. TelomeraseInhibitionbyInducedExpressionofAntisenseRNA. ............ 23 A. Muller,G. Saretzki,and1.vonZglinicki 5. Ex Vivoandin Vivo IGF-IAntisenseRNAStrategiesforTreatmentofCancerin Humans. . 27 D. D. Anthony,Y. X. Pan,S. G. Wu,F. Shen,andY.1.Guo 6. UseoftheIGF-IAntisenseStrategyintheTreatmentoftheHepatocarcinoma 35 LiaC. Upegui-Gonzalez,Huynh1.Due,YvesBuisson,MichelArborio, ChristianeLafarge-Frayssinet,ClaudeJasmin,YajunGuo,and JerzyTrojan 7. FunctionalInvolvementofCD44,aFamilyofCellAdhesionMolecules,in ImmuneResponses,TumourProgressionandHaematopoiesis .......... 43 U.Gunthert,C. Schwarzler,B.Wittig,1. Laman,P. Ruiz, R. Stauder, A. Bloem,F. Smadja-Joffe,M. Zoller,andA. Rolink 8. TheInfluenceofCD44SpliceVariantstotheOutcomeofPatientswithOral SquamousCellCarcinoma 51 C. Stoll,G. Baretton,F. Soost,andU. Lohrs ix x Contents 9. ControlofTumorGrowth viaInhibitionofTumorAngiogenesis 57 KarlH. Plate 10. ExpressionofCollagenase-3 (MMP-13)byTumorCellsin SquamousCell CarcinomasoftheHeadandNeck. ............................... 63 V-M. Kahari,N. Johansson, R. Grenman, K. Airola,andU. Saarialho-Kere II. High Level ExpressionofTissueInhibitorsofMetalloproteinases-I,-2 and -3 in MelanomaCellsAchievedbyAdenovirusMediatedGeneTransfer ...... 69 M. Ahonen,A. H. Baker,andV-M. Kahari 12. TissueInhibitorofMetalloproteinaseExpression: ATargetforGeneTherapyin Renal CellCarcinoma .......................................... 73 A. M. McElligott,A. H.Baker,andH. McGlynn 13. In Vivo TumorSuppressorEffectofRetrovirus-MediatedGeneTransferofthe Adenovirus ElaGene. ......................................... 79 R. Sanchez-Prieto,M.Quintanilla,A. Cano,M. Lleonart,P. Martin,and S. RamonyCajal 14. AntitumorEffectofEIBDefectiveAdenovirusesin HumanMalignantCells. .. 87 P. MartinDuque,C.Alonso, R. Sanchez-Prieto,M. Lleonart,and S. RamonyCajal 15. InhibitionofHumanPancreaticCancerGrowthbytheAdenovirus-Mediated IntroductionofaNovelGrowthSuppressingGene,tob, in Vitro 91 H. Yanagie,H. Sumimoto,Y.Nonaka,S. Matsuda,I. Hirose,S. Hanada, H.Sugiyama,S.Mikamo,Y.Takeda,I.Yoshizaki,K.Nakazawa, K.Tani, T. Yamamoto,S. Asano, M. Eriguchi,andT. Muto ChemogeneTherapy 16. Intratumoral InjectionofEncapsulatedCellsProducinganOxazaphosphorine ActivatingCytochromeP450forTargetedChemotherapy 97 PeterKarle, PetraMuller,RenateRenz, RalfJesnowski, RobertSaller, Kerstin vonRombs,HorstNizze,StefanLiebe,WalterH. Gunzburg, BrianSalmons,and MatthiasLohr 17. SensitisationofHumanOvarianCancerCellsto KillingbytheProdrugCB1954 FollowingRetroviralorAdenoviralTransferoftheE. coliNitroreductase Gene 107 P. F. Searle, S.1. Weedon,I.A. McNeish, M. G.Gilligan,M.1. Ford, F.Friedlos,C. J. Springer,L. S.Young,and D.1.Kerr 18. HSY-I ThymidineKinaseGeneTherapyfor PeritonealCarcinomatosis 115 C.Lechanteur, F. Princen, S. Lo Bue,B. Detroz,G. Fillet,1.Gielen,V Bours, andM.-P. Merville 19. CharacteristicsofCytosineDeaminase-5-FluorocytosineSystem: Enhancement ofRadiationCytotoxicityand BystanderEffect. ..................... 121 J. Szary, E. Missol,andS. Szala Contents xi 20. Potentiationofthe BystanderEffectbyImmunizationCombinedwith Suicide GeneTherapy 125 Rajagopal Ramesh,Aizen1.Marrogi,AnupamaMunshi,and ScottM. Freeman 21. AnotherMechanismCausingthe BystanderEffectBesidestheGapJunction's RoleduringtheGliomaGeneTherapywith HSV-TK/GCVSystem. ..... 133 LipingDu, ShaochunBai,Ian R. Whittle,andLinHe 22. In Vivo EvaluationofaDrug-InducibleVectorSystemfortheCombinedGene- andChemotherapyofCancer 139 W. Walther, U. Stein,1.Fichtner,H.Naundorf,M. Alexander, R. H. Shoemaker,andP. M. Schlag 23. IL-2GeneTransferforChemosensitizationofMultidrug-ResistantHuman ColonCarcinomaCells. ........................................ 145 UlrikeStein,WolfgangWalther,Robert H. Shoemaker,andPeterM. Schlag 24. CytotoxicEffectofBinarCisplatinImmunoconjugate 151 V. M. Plotnikov 25. DietaryIndoleDerivativesInduceApoptosisinHumanBreastCancerCells 153 FuadA. Fares,XiaokangGe,ShmuelYannai,andGadRennert TumorImmunology 26. OvercomingTCell IgnorancebyProvidingCostimulation: Implicationsforthe ImmuneResponseagainstCancer 159 LiepingChen 27. ImmuneCellsintheTumorMicroenvironment: MechanismsResponsiblefor Functionaland SignalingDefects ................................. 167 TheresaL. Whiteside 28. DendriticCellsPreventCD95 MediatedTLymphocyteDeaththrough CostimulatorySignals .......................................... 173 P.T. Daniel,C. Scholz,1. Westermann,B. Darken,andA. Pezzutto 29. Interleukin-IOInhibitstheImmuneStimulatoryPotentialofMelanomaCells RetrovirallyTransducedwith HumanB7.1 orB7.2 ................... 179 R. Geertsen,F.-Y. Vue,1. Pavlovic,E. Laine,andR. Dummer 30. ImmunosuppressiveCellsinBoneMarrowofPatientswith StomachCancer. .. 189 S. A. Kusmartsev,1. N. Kusmartseva,S.G.Afanasyev,and N. V.Cherdyntseva 31. InductionofAntigen-SpecificTCellsbyAllogeneicCD80TransfectedHuman CarcinomaCells 195 G. C. Meyer,U. Moebius, W. Rudy, R. Batrla,S.CMeuer,D.Wallwiener, andB. Giickel
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