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SYMPOSIUM
IITM Perspectives Meeting: Biologics as Therapeutics19TH SEPTEMBER 2018, MSTC
2 | IITM Perspectives Meeting: Biologics as Therapeutics
WELCOME
Welcome to the first Perspectives meeting of the Wellcome Trust Infection Immunology and Translational Medicine (IITM) DTC. These meetings will be held every two years, and aim to provide state-of-the-art talks on topics relevant to the IITM course.
We start with the exciting area of the development of ‘Biologics as Therapeutics’. There has been an explosion of interest in harnessing the immune system and its components to treat infectious, autoimmune, and neoplastic conditions. The meeting brings together leaders from industry and academia who have been at the forefront of exploiting biologics, as well those who are involved in funding the development of novel therapeutics. We are extremely grateful to all the speakers for giving up their valuable time to participate in this inaugural Perspectives meeting, and look forward to a stimulating day.
Professor Christoph Tang Director of the IITM Programme
Symposium 2018 | 3
PROGRAMME
9.00 Welcome & Session 1 Herman Waldmann, Mariagrazia Pizza
10.40 Coffeebreak
11.15 Session 2 GavinScreaton,ShaunCordoba
12.25 Open lunch (provided)
13.25 Session 3 RoundTableDiscussion StephenOakshott,SaraMarshall,BonnievanWilgenburg.Kerry Fisher
14.45 Coffeebreak
15.20 Session4 AusraRazanskiene,RichardPleass
16.30 Closingremarks
4 | IITM Perspectives Meeting: Biologics as Therapeutics
Professor Herman Waldmann PIattheSirWilliamDunnSchoolofPathology
Title of TalkReprogrammingoftheImmunesystem
SubjectThemAbCAMPATH-1Hwaslicensedforthetreatmentofrelapsing-remittingformsofmultiplesclerosisfouryearsago.Howeverworkonthisantibodybeganmorethanthreedecadesbefore,andstemmedfromfundamentalresearch on immune regulation and tolerance.
AhybridomawasisolatedthatproducedthemAb,CAMPATH-1,thatspecificallyrecognisestheglycoproteinCD52onhumanlymphocytes.SubsequentstudiesdemonstratedthatthemAbcouldfixhumancomplementandalsoeliminatelymphocytesinvitro.ThemAbwassuccessfullyengineeredforuseinhumans,andhasbeengiventopreventgraft-versus-host disease and transplant rejection, and toreversearangeofimmunedisorders.
Asidefromprovidinginsightsintotheregulationoftheimmunesystem,thedevelopmentandclinicaluseofCAMPATH-1havebeeninstructiveaboutthechallengesofturningscientificdiscoveriesintonoveltherapies.
BiographyHermanWaldmannisEmeritusProfessorofPathologyinOxford,recentlyretiredasHeadoftheSirWilliamDunnSchoolofPathology.Hismaininterestshavebeentoharnessthebody’sowntoleranceprocessestherapeuticallyforacceptanceoftransplantsandreversalofautoimmunediseases.Hislaboratorywasresponsibleforthe discovery and academic development oftheCAMPATH-1antibodiesculminatinginthelicensingofAlemtuzumab/Lemtrada.CurrentresearchfocusesonmechanismsbywhichregulatoryT-cellsmediatedominant(infectious)tolerance.HehasbeenaFellowoftheRoyalSocietysince1990,andwasafoundingFellowoftheAcademyofMedicalSciencesin1998.In2008,hewasawardedanHonoraryDoctoratefromtheUniversityofCambridge.
Symposium 2018 | 5
Dr Mariagrazia Pizza SeniorScientificDirectorBacterialVaccines,GSKVaccines,Siena,Italy
Title of TalkNoveltechnologiesforthedevelopmentofnewtherapeuticvaccines
SubjectTechnologicalrevolutionshaveenabledthedevelopmentofnovelvaccinesandisexpectedtodelivervaccinesagainstotherinfectiousconditions,suchasantibiotic-resistantbacteria,chronicandrecurrentinfections.
Reverseandstructuralvaccinology,combinedwithsyntheticbiology,systemsbiology,andnoveladjuvants,arethebeginningofanewerain vaccinology. Additionally, the immune system cancontrolandeliminatechronicinfectionsand tumours so vaccination could, alone or incombinationwithimmunotherapy,elicitprotectiveimmuneresponses.Forexample,theimmunesystemcancureHIV,basedonpassiveimmunizationwithbroadlyneutralizingmonoclonalantibodies,whichrapidlyreduceviremiatoundetectablelevels.Thereforeresponsesinducedbyvaccination,couldhelpcurechronicallyinfectedpeople.
AnelegantexampleisprovidedbythenovelvaccineagainstHerpesZoster(HZ),whichcanrestore cell mediated and humoral immunity againstVaricellaZosterVirus(VZV).Thisvaccine,composedbytheVZVgEantigenwithAS01,anadjuvantthatboostscellularandhumoralresponses,has>90%efficacyinallagegroups.
BiographyMariagrazia Pizza received her degree in Chemistry andPharmaceuticalTechnologiesattheUniversityofNaples,Italy.FollowingaperiodattheEMBOlaboratoriesinHeidelberg,Germany,shemovedtoSiena,Italywhereshehasbeeneversinceleadingmanybacterialprojects.Shecontributedtothediscoveryofapertussisvaccinebasedonageneticallydetoxifiedtoxin,andtothediscoveryofanewvaccineagainstMeningococcusB,licensedinmanycountriesworldwide.MariagraziaiscurrentlySeniorScientificDirectorforBacterialVaccinesatGSKVaccines,inSiena.ShehasreceivedmanyscientificawardsandisanelectedmemberofEMBO,theEuropeanAcademyofMicrobiology,FellowoftheAmericanAcademyofMicrobiologyandVicePresidentofIUMS(InternationalUnionofMicrobiologySocieties).MariagraziaisalsoHonoraryVisitingProfessorattheUniversityofLeicester.Shehasover190publicationsininternationalpeer-reviewedjournalsandisco-inventorofmanypatents.
6 | IITM Perspectives Meeting: Biologics as Therapeutics
SubjectDengueisamosquitoborneviralinfectionoccurringintropicalandsubtropicalcountries.Thereareestimatedtobearound400millioninfectionsannually.Themajorityoftheseareself-limiting,but1-5%ofinfectionsleadtodenguehaemorrhagicfever,characterizedbyvascularleak,andinextremecasesshockandhaemorrhage.Dengueexistsasfourhighlydivergentserotypes;infectionwithoneserotypedoesnotprovideprotection against the other three. Interestingly, severe disease is much more common in secondaryasopposedtoprimaryinfections,implyingaroleoftheacquiredimmunesystemindiseasepathogenesis.Understandingimmuneenhancementiscrucialfordesigningsafe,effectivevaccines.ThroughcollaborationsinThailandandVietnamwehavebeendetailingimmuneresponsestodengueinchildren.IwilldescribeantibodyresponsestothesurfaceglycoproteinsprMandE,andtheEdimerepitope(EDE),anovelsitebridgingthe90dimersmakingupthevirionsurfaceandalsocrossreactsagainstZikavirus.
Professor Gavin Screaton HeadofMedicalSciences Division,OxfordUniversity
Title of TalkThehumanantibodyresponseindengueandZikavirusinection
BiographyProfessorScreatonreceivedhisfirstdegreefromCambridgein1984beforemovingtoOxfordtocomplete his medical studies in 1987. He then completed training in general internal medicine andobtainedaDPhilfromOxfordUniversityin1998.In2004,ProfessorScreatonwasappointedtotheChairofMedicineatImperialCollege.HereturnedtoOxfordasHeadoftheMedicalSciencesDivisioninOctober2017.
Hisresearch,whichhasbeensupportedbyaseriesofFellowshipsawardedbytheMRCandWellcomeTrust,hascoveredavarietyoftopicsfromcontrolofRNAprocessingandapoptosistoimmunology.ThecurrentinterestsofhislaboratoryrevolvearoundtheimmunologyofinfectiousdiseaseswithaspecialinterestindenguehaemorrhagicfeverandZika,wherehisresearchiscurrentlyfundedbytheWellcomeTrust,withactiveresearchcollaborationsinSouth-EastAsia.
Symposium 2018 | 7
Dr Shaun Cordoba DirectorofSyntheticBiologyatAutolusTherapeutics
Title of TalkImmunotherapy:EngineeringTcellsforthetreatment
SubjectTherehavebeendramaticrecentadvancesinimmunotherapy,byengineeringTcellsforthetreatmentofcancer.Iwilloutlinecurrentstrategies, and latest immunotherapeutic approaches,andhighlightpre-clinicaldatausing a Chimeric Antigen Receptor.
BiographyIamcurrentlytheDirectorofSyntheticBiologyatAutolusTherapeuticswhereIdevelopChimericAntigenReceptors(CARs)forthetreatmentofcancers.IdidmyPhDattheUniversityofSydney,examininggeneexpressionprofilesinimmunecellsfrompatientsundergoingtransplantation.Ihaveheldpost-doctoralappointmentsattheUniversityofOxfordandImperialCollegeLondononTcellandNKcellactivation.
Bonnie van Wilgenburg Analyst,lifescienceventurecapitalfirmForbion
BiographyBonnievanWilgenburgisananalystatForbion,aleadingventurecapitalfirmthatworkscloselywithscientistsandentrepreneurstobuildlifesciencescompanies.Bonnie’sworkinvolvessourcingnewinvestment opportunities, evaluatingbusinessplans,completing venture transactions andcontributingtoportfoliomanagement. Previously she workedasanacademicscientistpublishingsixfirst-authorpapersinthefieldsofimmunology,stemcell research and virology. As a Marie-CuriefellowandrecipientoftheRoyalSocietytravelgrantsheinvestigatedtheroleofinnateT-cellsinresponsetoviralinfectionsinthelaboratoriesofProf.Klenerman(UniversityofOxford)andProf.McCluskey(UniversityofMelbourne).
BiographySara joined Wellcome in 2016 as HeadofClinicalandPhysiologicalSciences.SheobtainedhermedicaldegreefromtheNationalUniversityofIreland,andworkedasajuniordoctorinDublinbeforegoingtoStanfordUniversity,CaliforniaasfellowinLungTransplantation. She held an MRCClinicianScientistawardattheUniversityofOxford,andwasthenaClinicalSeniorLectureratImperialCollegewhereherresearchinterestsfocusedonthegeneticsoftransplantationandinflammatorydiseases.Prior to joining Wellcome, shewasProfessorofClinicalImmunologyattheUniversityofDundee,whereshewasalsoDirectoroftheDundeeClinicalAcademicTrackandDeputyHeadofR&DforNHSTayside.
Professor Sara Marshall HeadofClinicalandPhysiologicalSciences, Wellcome Trust
Round Table
BiographySteveistheHeadofInnovativeTechnologies at the Medical ResearchCouncil(MRC),partofUKResearchandInnovation.His role at the MRC involves oversightofseveraloftheMRC’stranslationalresearchand industry liaison schemes andactivities,alongsideworkwithotherfundersonmajorgovernmentinitiativesliketheIndustrial Strategy Challenge Fund.Afterundergraduateand postgraduate studies at theUniversityofCambridge,StevemovedtoNewYork,initiallyasapost-doctoralresearcheratBrooklynCollege,CUNYandsubsequentlyasascientist at PsychoGenics, a preclinical research company.
Steve Oakeshott Medical Research Council (MRC)
Symposium 2018 | 9
Dr Kerry Fisher ChiefScientificOfficeratPsiOxusTherapeuticsandLecturer,OxfordUniversity
Title of TalkHarnessingoncolyticvirusesfortherapy
SubjectTranslatingcomplexbiologicaldrugcandidatesfromthelaboratorytoaclinicaltrialcanbechallenging.Thisisparticularlythecasefordeveloping oncolytic viruses as therapeutics, especiallywhenspeciesspecificityaffectsviralreplication and delivery, limiting the relevance ofanimalmodels.Thereisintenseinterestinunderstandinghowadministrationofoncolyticvirusescanbeintegratedintoourknowledgeoftumourimmunologyandheterogeneityto optimise therapeutic approaches.
BiographyKerryFisherhasbeenworkinginthefieldofoncolyticvirusesforover15yearsandisafoundingscientistofPsiOxusTherapeuticsandpreviouslyHybridSystems.HewasawardedaPhDintherapeuticgenedeliveryfromtheUniversityofBirminghamandhasspecializedinthesystemicadministrationofvirusesforthetreatmentofcancer. Heisparticularlyinterestedinhowvirusesreplicate,spreadandstimulateimmunecellswithinthetumourmicroenvironment.Kerry holds a research lectureship at the UniversityofOxfordandhaspublishedover60publicationsinthefieldofoncolyticvirusesandfiledover20patentapplications.
10 | IITM Perspectives Meeting: Biologics as Therapeutics
Dr Ausra Razanskiene ScientificManageratNomadsinVilnius,Lithuania
Title of TalkPlant-ExpressedAntimicrobialProteins
SubjectAntibioticshavebeencriticalincuringinfections;however,widespreaduseofantibioticshascausedtheemergenceantibiotic-resistantstrains.Withfewnewantibioticsinthepipeline,antibioticresistanceisaseriousglobalthreattopublichealth.
Plant-expressedcolicins,bacteriocinsnaturallyproducedbyE. coli thatkillorinhibitthegrowthofother E. coli strains,canbeeffectiveantibacterials.Colicin-likeproteinsfromKlebsiella(klebicins)and Pseudomonas aeruginosa (pyocins) can alsobeproducedinplants.Pyocinsexcellentlycontrol Pseudomonas pathovars in animal models.Therefore,colicin-likemoleculesareapromisingclassofantibacterials.Endolysinsarehydrolyticenzymesproducedbybacteriophagesduringthelyticphaseoftheirlifecycle,andhavebeenefficientlyexpressedinplants,withsomeproductsinclinicaltrialsandonthemarket.
Commercializationofbacteriocinsandendolysinscouldgenerateapipelineofnovelalternativestoantibiotics.Attractivecandidatescouldbeedibleand/ortopicalandrequireonlypartialpurification.
Biography1988-1992–biologystudiesinVilniusUniversity.
1992-1993-DEA(DiplomedesEtudesApprofondies)inPlantdevelopmentbiologyinParisVI(PierreetMarieCurie)University.
1993-1998-PhDstudiesinParisVIinPlantdevelopmentbiology,incollaborationwithInstitutdesSciencesVegetales(Gif-sur-Yvette),CNRS.
Since1998–scientist,laterseniorscientistinInstituteofBiotechnologyinVilnius(currentlyInstituteofBiotechnology,LifeScienceCenter,VilniusUniversity).Maininterest:recombinantexpressionofvirussurfaceandnucleocapsidproteins in yeast and plants and their applicationsfordiagnosticandvaccines.
Since2010–manageratUABNomads(daughtercompanyofNomadBioscienceGmbH).Thecompanyspecializesinplanttransientexpressionsystems.Wearecurrentlyfocussingonproductionofantimicrobialproteins,bacteriophagelysinsandbacteriocins.
Symposium 2018 | 11
Professor Richard Pleass ProfessorofParasitology,LiverpoolSchoolofTropicalMedicine
Title of TalkN-terminalhingeglycosylationfornovelreceptor interactionsofIgGFcmonomersandmultimers
SubjectInneurology,intravenousimmunoglobulin(IVIG)servesasamainstaytherapyinimmune-mediatedneuropathies,includingchronicinflammatorypolyneuropathy(CIDP)andGuillain-Barresyndrome.
TheworldwideconsumptionofIVIGhasincreasedover300foldsince1980andcurrently~100tonsareconsumedperannum.SuppliesofIVIGwithintheNHSandgloballyarecriticallylimited,meaningthatpatientswithanurgentneedforthedrugareroutinelydeprivedofit.Therearesignificantclinicallimitationsresultingfromitsdependenceonhumandonorsformanufacture,andfromthefactthat<5%ofinjectedIVIG(correctlyglycosylated Fc) is therapeutically active, leading toarequirementforhighdoses(2g/kg)whenusedtotreatinflammatoryconditions,includingCIDP.Consequently,IVIGisexpensiveandadverseeventsduetoexcessiveproteinloadingarenotuncommon.ThechallengesassociatedwithmanufacturingandapplicationofIVIGrepresentanincentivetodevelopmoleculeswithimprovedefficacy,thesubjectofthepresentation.
BiographyAspartofmyWellcomeTrustfellowshipIdevelopedthefirstfullyhumanantibodiestargeting the malaria parasite, and have experienceingeneratingantibody-basedstructuresfornewapplications.
Ourrecentresearchhasfocussedoncreatingmultimericantibody-Fcplatformsforthedevelopmentofnewdrugsandvaccines.
ThistechnologywasrecognisedbytheawardoftheUniversalBiotechInnovationprizein2013andwasshortlistedfortheBionowProjectoftheYearin2014.
Despitetheseexcitingdevelopments,muchbasicsciencehasyettobeperformedtotakethesemoleculesintolessexploredareas.
iitmoxford.com
About IITM Programme
TheIITMDPhilprogrammeisfundedbytheWellcomeTrust and gives students the opportunity to complete three3-monthlaboratory-basedresearchprojectsindifferentlabsacrosstheuniversityduringtheirfirstyear.Attheendofthefirstyear,studentsthenchooseoneormoreoftheselabsinwhichtocompletetheirDPhilthesisprojectfortheremainingthreeyears.
TheprogrammeisdirectedbyProfessorChristophTang(Director)andProfessorHelenMcShane(Co-director).
Acknowledgements
TheIITMSymposiumisgenerouslysupportedbytheWellcomeTrust.ManythankstoDawnGibbons(theIITMcourseadministrator)fororganisingtoday’smeeting.
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