News About the Stanford BMT Programbmt.stanford.edu/content/dam/sm/bmt/documents/... ·...
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STANFORD BMT UPDATE bmt.stanford.edu News About the Stanford BMT Program A?er an@body treatment against c- Kit and CD47, the host hematopoie@c stem cells were deleted, pending acceptance of allogeneic stem cells from a donor source (see Page 3 for story). THE HIGHLIGHTS Pa+ent’s own T-cells are used to produce chimeric an+gen receptor (CAR) CAR combines the targe+ng part of an an+body and signaling part of the T- cell receptor cancer since it can go directly to the targeted cancer cells. Therapeu@c monoclonal an@bodies have come to frui@on such as rituximab for lymphoma and hercep@n for breast cancer. However, monoclonal an@body therapy alone did not fulfill its original promise. On the other hand, the cellular arm of the immune system has shown to be even more effec@ve against cancer cells. One such example is allogeneic transplant where donor T-cells eliminate residual cancer cells, resul@ng in a cure in many different kinds of hematologic malignancies. However, this process is not precise and off-target killing occurs in the form of gra?-versus-host disease (GVHD). One way to bring these two poten@ally powerful an@-cancer therapeu@cs together is by W hen Kohler and Milstein developed hybridoma technology in 1975, a monoclonal an@body was thought to be the “Magic Bullet” to treat arming the T-cells with a monoclonal an@body that recognizes molecule(s) on the cancer cells. Thus far, the most successful approach is the chimeric an@gen receptor (CAR) T-cells. In The Modern-Day Magic Missile: Arming the T-Cells with Cancer-Targe+ng An+body this strategy, the pa@ent’s own T-cells are gene@cally engineered to produce a hybrid molecule (the CAR) on these tumor-killing cells. The extracellular por@on of the CAR molecule is composed of the an@gen-recognizing part of a monoclonal an@body, while the intracellular por@on contains the ac@va@ng mo@fs of the T-cell receptor. When CAR T-cells are infused into the body, the an@gen-recognizing part brings these cells to the targeted cancer cells and FALL 2016 Stuart Brinin Photography con1nued on page 4 3 BENCH TO BEDSIDE Disrup’ve Innova’on 5 TRANSLATIONAL RESEARCH Cellular Therapeu’cs 6 CLINICAL STORY It Takes a World to Cure a Cancer 8 OUR VISION Build a Cellular Therapeu’cs Powerhouse
Transcript of News About the Stanford BMT Programbmt.stanford.edu/content/dam/sm/bmt/documents/... ·...
STANFORDBMTUPDATEbmt.stanford.edu
NewsAbouttheStanfordBMTProgram
A?eran@bodytreatmentagainstc-KitandCD47,thehosthematopoie@cstemcellsweredeleted,pendingacceptanceofallogeneicstemcellsfromadonorsource(seePage3forstory).
THEHIGHLIGHTS
Pa+ent’sownT-cellsareusedtoproducechimerican+genreceptor(CAR)
CARcombinesthetarge+ngpartofanan+bodyandsignalingpartoftheT-cellreceptor
cancersinceitcangodirectlytothetargetedcancercells.Therapeu@cmonoclonalan@bodieshavecometofrui@[email protected],monoclonalan@bodytherapyalonedidnotfulfillitsoriginalpromise.Ontheotherhand,thecellulararmoftheimmunesystemhasshowntobeevenmoreeffec@veagainstcancercells.OnesuchexampleisallogeneictransplantwheredonorT-cellseliminateresidualcancercells,resul@nginacureinmanydifferentkindsofhematologicmalignancies.However,thisprocessisnotpreciseandoff-targetkillingoccursintheformofgra?-versus-hostdisease(GVHD).Onewaytobringthesetwopoten@allypowerfulan@-cancertherapeu@cstogetherisby
W henKohlerandMilsteindevelopedhybridomatechnologyin1975,amonoclonalan@bodywasthoughttobethe“MagicBullet”totreat
armingtheT-cellswithamonoclonalan@bodythatrecognizesmolecule(s)onthecancercells.Thusfar,themostsuccessfulapproachisthechimerican@genreceptor(CAR)T-cells.In
TheModern-DayMagicMissile:ArmingtheT-CellswithCancer-Targe+ngAn+body
thisstrategy,thepa@ent’sownT-cellsaregene@callyengineeredtoproduceahybridmolecule(theCAR)onthesetumor-killingcells.Theextracellularpor@onoftheCARmoleculeiscomposedofthean@gen-recognizingpartofamonoclonalan@body,whiletheintracellularpor@oncontainstheac@va@[email protected],thean@gen-recognizingpartbringsthesecellstothetargetedcancercellsand
FALL2016
StuartBrininPhotography
con1nuedonpage4
3 BENCHTOBEDSIDEDisrup've Innova'on
5 TRANSLATIONALRESEARCHCellular Therapeu'cs
6 CLINICALSTORYIt Takes a World to Cure a Cancer
8 OURVISIONBuild a Cellular Therapeu'cs Powerhouse
StanfordBloodandMarrowTransplantProgram300PasteurDriveRoomH0101Stanford,CA94305ToReferAPa+ent:Phone:650.723.0822Faculty:RobertNegrin,MDProgramDirectorSallyArai,MD,MSWesBrown,MDLauraJohnston,MDRobertLowsky,MDEveregMeyer,MD,PhDDavidMiklos,MD,PhDLoriMuffly,MD,MSAndrewRezvani,MDJudithShizuru,PhD,MDWen-KaiWeng,MD,PhDNP/PA:RimaBoushakraConnieChenRichardDibellaMaricrisDacumosErinFrawleyMaiXiongGillinghamTracyMurrayLynnO’NeillHeatherRadfordMaureenRyanBrookSmithSarahStengerAdministra+veDirector/DivisionAdministratorLauraAdamsWebsite:bmt.stanford.eduNewsleSerEditor:Wen-KaiWeng,MD,PhD
THEDIRECTORFILE
outstandingcompassionatecarethatweprovideourpa@entswhileconduc@ngstateoftheartbasicandtransla@onalscienceonstemcellbiology,cellularimmunologyandtransplanta@onbiology.OurProgramisfocusedonthecomprehensiveevalua@onandcareofpa@entswithcomplexhematologicalmalignanciesandotherbonemarrowfailuresyndromeswherebloodandmarrowtransplanta@oncanprovidebenefit.
W elcometotheDivisionofBloodandMarrowTransplanta@on.Weareveryproudofthe
Ourprogramhasprovidedtransplanta@onservicestoover5,[email protected],fellows,residents,nurseprac@@oners,physicianassistants,anexpertnursingstaffaswellasotheralignedstaffwhoworktogethertoprovidethebestpossiblecareforourpa@entsundergoingtreatmentatStanfordduringthis@meoftheirgreatesthealthchallenge.Ourfacultyperformscujngedgeresearchexploringthebasicbiologyofhematopoie@cstemcellsandeffectorTcellssuchasnaturalkillercells,regulatoryTcells,cytotoxicTcellsandBcellswiththeaimofexploringtransla@onalresearchopportuni@eswhereverpossible.WearesupportedbygrantsfromtheNa@onalIns@tutesofHealthincludingaProgramProjectGrantnowinthe25thyearoffundingaswellasfounda@onsupportfromins@tu@onsliketheCaliforniaIns@tuteofRegenera@veMedicineandtheNa@onalMarrowDonorProgram.TheDivisionrunstheBoneMarrowTransplantCellularTherapeu@csFacilitywhereallclinicalmaterialispreparedfortransplanta@onandwherecomplexcellsepara@onandexpansionprotocolscanbeaccomplished.Weprideourselvesintrainingphysicianscien@stsandperformingtransla@onalresearchtofindbegerapproachesforthetreatmentofourpa@entsandadvancementofthefield.Wewelcometheopportunitytoserveyourpa@entsandarealwaysavailableforconsulta@onandreferral.Thankyoufortheopportunityandtrustinprovidingthebestpossiblecaresupportedbythestrongestscienceforyourpa@ents.RobertS.NegrinMDProfessorofMedicineandDivisionChief
Disrup+veInnova+on:An$body-OnlyAllogeneicTransplanta$on
hematologicmalignancies,orinheriteddisorderssuchasseveralformsofimmuno-deficiency,thetransplant-relatedsideeffectsandcomplica@onsremainthebiggesthurdles.Oneofthesourcesforsideeffect/complica@onisthecondi@oningregimenpa@entsreceivepriortothedonorgra?infusion.Thecondi@oningregimenisusuallycomposedofacombina@onofchemotherapieswithorwithoutradia@on,andisdesignedtogetridofthehematopoie@ccellsintherecipientsothedonorhematopoie@ccellscantakeahold(engra?ment)a?erinfusion.Inaddi@on,thedonorgra?susuallycontainmaturebloodcells(T-cells,B-cells,NKcells),whicharenecessarytofacilitateengra?ment.However,thesematuredonorbloodcellscanalsocausegra?-versus-hostdisease(GVHD).
Ideally,transplantsshouldbeperformedusingachemotherapy/radia@on-freecondi@oningregimenwithpurifieddonorhematopoie@cstemcellswithoutmaturebloodcells.Inthisscenario,pa@entscouldavoidthetoxici@esbroughtbytradi@onalcondi@oningandtheGVHDcausedbymaturedonorbloodcellscarriedoverinthestandardgra?.Itturnsoutthatthisisnotaneasytask.Forsuccessfuldonorcellengra?ment,twoobstaclesmustbeovercome.First,therecipientimmunesystemhastobecontainedsoitwillnotrejecttheincomingdonorcells.Second,thedonorhematopoie@ccellsmustbeabletoenterthenichespaceintherecipientbonemarrow.InDr.JudithShizuru’slaboratory,effortsweredevotedtofindingan@bodiesthatcandeplete
therecipienthematopoie@cstemcellsinthebonemarrowtoopenthenicheforthedonorcells.A?erextensivetes@ngofdifferentmoleculesonthestemcells,theyfoundthatmonoclonalan@bodiesagainstc-Kit(CD117)areabletoachievethatgoal.Inananimalmodel,an@-c-Kitan@bodyalonewassufficienttopromotesuccessfulengra?mentofpurifieddonorstemcellsinimmuno-compromisedmice.Intheseanimals,therewerelimitednumberofimmunecellstorejectthedonorstemcells.However,asexpected,an@-c-Kittreatmentaloneisnotenoughforstemcellsengra?mentinimmune-competentmiceduetotherobustrecipientimmunecells.Toovercomethatchallenge,Dr.Shizuru’steamusedanaddi@onalan@[email protected]@onofan@-c-Kitandan@-CD47,purifieddonorstemcellscansuccessfullyengra?inimmuno-competentmicewithoutanyothertreatment.Intheseanimals,noGVHDwasobservedsincenomaturedonorbloodcellswereinfused.Whilethisisonlyapre-clinicalstudy,[email protected]@veinnova@ontopa@entcare,aphaseIstudyhasrecentlybeenopenedtotreatchildrenwithseverecombinedimmunodeficiency(SCID)usingan@-human-c-Kitan@[email protected],“Iwanttomakethetransplanta@onprocedureanorderofmagnitudesafer,andtoachievetheend-goalthatcurescancer,immunodeficiencyandautoimmunedisease.
W hileallogeneictransplanta@oncanbelifesavingforpa@entswith
BENCHTOBEDSIDE
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[email protected],CART-cellswillbeac@vatedtokillthetargetedcancercells.SinceFebruary2016,7pa@entswithrefractorydiffuselargeB-cellhavereceivedCD19-CART-cellstarge@ngtheCD19moleculeonthelymphomacells.Whilesomeexperiencedsignificanttherapy-relatedsideeffects,allrecoveredfullywithseveralpa@entsachievingtremendoustumorshrinkageasdemonstratedinonesuchexampleshownbelow.
TofacilitateclinicaltrialsemployingcellularimmunotherapiessuchasCART-cells,Dr.CrystalMackall,directoroftheStanfordCancerImmunotherapyProgram,willworkcloselywithfacultymembersinBMTtodevelopnovelcancercellularimmunotherapies.
TheModern-DayMagicMissileHematopoie@cstemcelltransplanta@oninimmunocompetenthostswithoutradia@onorchemotherapy.SCIENCETRANSLATIONALMEDICINEAChhabra,AMRing,KWeishopf,PJSchnorr,SGordon,ACLe,H-SKwon,NGRing,JVolkmer,STseng,ILWeissman,JAShizuru2016;8(351):351ra105
Presensi@za@ontoHYan@gensinfemaledonorspriortotransplantisnotassociatedwithmalerecipientpost-transplantHYan@bodydevelopmentnorwithclinicaloutcomes.HAEMATOLOGICAHNakasone,BSahaf,LTian,TWang,MDHaagenson,KSchoenrock,SPerloff,CERyan,FWu,SRSpellman,SJLee,JRitz,DBMiklos,CIBMT2016;101(1):e30-e33
Psychologicalmorbidi@esinadolescentandyoungadultbloodcancerpa@entsduringcura@ve-intenttherapyandearlysurvivorship.CANCERLSMuffly,FJHlubocky,NKhan,KWroblewski,KBreitenbach,JGomez,JLMcNeer,WStock,CKDaugherty2016:122(6):954-961
ArandomizedphaseIIcrossoverstudyofima@niborrituximabforcutaneoussclerosisa?erhematopoie@[email protected],JPidala,IPusic,XChai,SJaglowski,NKhera,JPalmer,GLChen,MHJagasia,SAMayer,WAWood,MGreen,TSHyun,YInamoto,BEStorer,DBMiklos,HMShulman,PJMar@n,SSarantopoulos,SJLee,MEFlowers2016;22(2):319-327
Allogeneichematopoie@ccelltransplantfornormalkaryotypeAML:Indirectevidenceofselec@onforadversemolecularprofile.BONEMARROWTRANSPLANTATIONMEPervival,BCMedeiros,SRobeson,GGLaport,LJJohnston,JAShizuru,DBMiklos,SArai,WKWeng,RSNegrin,RLowsky2015;50(7):1004-1006
Third-partyCD4+invariantnaturalkillerTcellsprotectfrommurineGVHDlethality.BLOODDSchneidawind,JBaker,APierini,CBuechele,RHLuong,EHMeyer,RSNegrin2015;125(22):3491-3500
Risksandbenefitsofsex-mismatchedhematopoie@ccelltransplanta@[email protected],MRemberger,LTian,PBordin,BSahaf,FWu,JMagsson,RLowsky,RSNegrin,DBMiklos,EHMeyer2015;100(11):1477-1485
Allogeneichematopoie@ccelltransplanta@ona?erfailedautologoustransplantforlymphomausingTLIandan@[email protected],ASKanate,BEfron,SChhabra,HEKohrt,JAShizuru,GGLaport,DBMiklos,JEBenjamin,LJJohnston,SArai,WKWeng,RSNegrin,,SStrober,RLowsky2015;50(10):1286-1292
con1nuedfromcover
Dr.DavidMiklosleadsthewayintroducingtheclinicaltrialswithCART-celltherapeu1csatStanford.Whiletheini1alstudywasforpa1entswithlymphoma,thisnewtechnologycanpoten1allybenefitpa1entswitha
varietyofhematologicmalignanciesandevensolidtumors.Dr.Mikloswillcon1nuetoworkwithDr.Mackalltodeveloparobustclinicalprogram.
SELECTEDRECENTPUBLICATIONS
PETinonepa@entshowedgreattumorreduc@on4weeksa?erCD19-CART-cellsinfusion.
2X106CARTCells/kg
TRANSLATIONALRESEARCH
controllingthedisease,diseaserelapseiss@lltheprimaryreasonthatpa@entsdonotdowella?eranallogeneictransplanta@on.Twostrategiesarecommonlydeployedinmanagingpost-transplantrelapses:reducingthetumorburdenbyappro-priatemeans,andheighteningthegra?-versus-tumoreffect.Theformerusuallyrequirestradi@onalchemotherapies,[email protected],thereareseveraldifferentwaystoheightenthedonorgra?func@on.Theseincludewithdrawalofimmunosuppression;immunes@mula@onwithimmunomodulatorssuchasCpG,interferonorcheckpointinhibitors;[email protected],wehaveaspecialinterestindonorcellulartherapeu@cs.
Theuseofdonorlymphocyteinfusions(DLI)hasbeenpivotalintrea@ngpost-transplantrelapse.TheefficacyofDLIdependsonthedoseoftheinfusedTcells.However,higherdosesofDLIarealsoassociatedwithhigherincidenceofgra?-versus-hostdisease(GVHD).TodissecttheroleofdifferentTcellpopula@ons,apre-clinicalmousemodelwasconductedatDr.SamuelStrober’slaboratory.Inaseminalreport(Blood2011;117:3230-3239),they
foundthatCD8+memoryTcellsweretheonlypopula@oncapableoferadica@ngcancercellswithoutinducingGVHD.Basedonthiscri@calobserva@on,Dr.RobertLowskystartedaclinicaltrialusingenrichedCD8+memoryTcellsasanalterna@vetoDLIinpa@entswhorelapseda?erallogeneictransplant.
InthisphaseItrial,15pa@entswithavarietyofdiseases(acutemyeloidleukemia,lymphoma,chroniclymphocy@cleukemia,chronicmyeloidleukemia,myeloma,andacutelymphoblas@cleukemia)receivedCD8+memoryTcellinfusionsatthreedoselevels.ThegoalistoinfuseahighdoseofdonorCD8+memoryTcellswithouttriggeringGVHD.Mostofthepa@ents(87%)receivedcytoreduc@vetherapypriortoCD8+memoryTcellinfusion.Fivepa@entsreceivedthehighestplanned10x106/kgdose.Asexpected,therewerenosevereadverseeventsa?erinfusion,andnodose-limi@[email protected]@ent,waslimitedtogradeIIinvolvementoftheliver,andresolvedfollowingacourseofsteroids.Tenpa@ents(67%)maintainedorachievedresponse(7completeresponse,1par@alresponse,2stabledisease)includingoneacutelymphoblas@cleukemia
W hilethegra?-versus-tumoreffectprovidedbythedonorgra?canbeverypowerfulin
CellularTherapeu+cs:HarnessthePowerofthe“Good”CellularComponent
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pa@entwhohasrespondedtoCD8+memoryTcellsalonewithoutanyothertherapy(seele?).
Thisisoneexampleofour@relesscommitmenttounderstandingthefunc@onofcri@calcellularcomponentsfromthedonorgra?,andoureffortstotranslateourresearchintoclinicalprac@cetoadvancethequalityofpa@entcare.
Threelogreduc@onofcircula@ngleukemiaburdena?ersingledonorCD8+memoryTcellinfusioninapa@entwithrelapsedacutelymphoblas@cleukemiaa?erallogeneictransplant.
CLINICALSTORY
(leP)RobinwithSarahinGermany.(right)Robinwithher“Chimera”,thestuffedanimalshehadmadetosymbolizeherstory.
ItTakesaWorldtoCureaCancer
knewthatitwouldbealongjourneyforherfightagainstthiscancer.Giventhedysplas@cchangesinherbonemarrow,standardchemotherapieswereunlikelytogiveheralong-termremissionoracure.Herbestchancewastoreceiveanallogeneic(donor)transplant.However,neitherofhersiblingswereamatchtoher.Theonlyop@onwastofindasuitablematcheddonorthroughtheNa@onalMarrowDonorProgram(NMDP).First,Robinhadtoundergoseveralroundsofchemotherapypriortobeingconsideredfortransplant.ByJune2012,shewentintoclinicalremissionandlearnedthatone(theonlyone)10/10fullymatcheddonorhadbeeniden@fiedthroughtheNMDP.
Robinthenreceivedthecondi@oningregimen,followedbydonorcellinfusioninlateJuly.Atthe@meshereceivedherlife-savingcells,sheonlyknewthattheywerefromayoungwomanwholivesinEurope.Eventhoughshewass@llstrugglingwithimmediatepost-transplantsideeffects,shemanagedtowritethank-younotesinAugust,[email protected],sherecoveredbitbybitandherleukemiawasgone.Althoughsheexchangedanonymouslegerswithherdonorafew@mes,theywerenotallowedtorevealtheirprivateinforma@onun@ltwoyearsa?ertransplant.Bytheendof2014,RobinfinallylearnedthatherdonorwasawomannamedSarahfromNorthernGermany.
[email protected],[email protected]?erafewmonthsofslowback-and-forthemails,RobinandSarahdeclaredtheirwishtomeetinperson,
andofcourse,inGermany.ArmedwithashortcourseinGerman,RobinandherhusbandflewtoHamburgintheFallof2015,beforedrivingtothesmallfarmvillagewhereSarahlived.Thefirstmee@ngoccurredatthehotellobbywhereRobinstayed.RobinandSarahlookedateachotherunbelievinglyandthencollapsedintoalongembrace.Thefollowingdays,SarahhostedRobinandherhusbandinherfamilyhome.Theyspent@mewithSarah’sandherhusband’sfamilies,touredneighboringvillagesandvisitedSarah’[email protected],thistripalsomeantsomeanswers.ThefirstonewashowSarahdecidedtojointhedonorprogram.Itturnedoutthatthereweretwoboysintheneighboringtownsneedingdonorsfortransplant,whichprompteddonordrivesintheprecedingyears.Unfortunately,neitherboyfoundasuitabledonor.RobinalsowantedtoknowwhySarahdecidedtodonateeventhoughshewasscaredandthe@mingwasnotideal.Sarah’sanswerwassomager-of-fact,“Whatelseistherethantohelpanotherhuman?”A?erthefour-dayreunionofthesetwolivesthathadintertwinedforeverthroughthislife-savingprocedure,Robinreturnedhomefeelingpeacefulandfulfilled.Tothisdate,RobinandSarahcon@nuetocommunicateonadailybasis.
Eachyear,StanfordBMTprogramperformsabout90-95allogeneictransplantswithhematopoie@cstemcellsfromanunrelateddonorjustlikeSarah.HavingasuitabledonorthroughtheNMDPcanmeanalife-savingevent.Currently,approximately27millionpoten@aldonorsareaccessibleeitherwithintheUnitedStatesnetworkorbyInterna@onalregistry.Ifyouareinterestedinbecomingapoten@aldonor,pleasevisitNMDPwebsiteathgp://BeTheMatch.org
W henRobinwasfirstdiagnosedwithacutemyeloidleukemiainDecember2011,she
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CarlosSilva,MD
receivedhismedicaldegreefromtheHealthScienceUniversityFounda@oninColombia.HecompletedInternalMedicineresidencyattheState
UniversityofNewYorkDownstateMedicalCenterandwasrota@nghousestaffatMemorialSloan-KegeringCancerCenterinHematologicalmalignanciesandBoneMarrowTransplant.HedidhisHematologyandOncologyfellowshipatCaseWesternReserveUniversity/CaseComprehensiveCancerCenter,whereheservedasChieffellow.HisclinicalresearchinteresthasbeenfocusedonLymphoidmalignanciesandtransplanta@on.Someofhisworkwasrecentlypresentedatthe2016ASBMTannualmee@ng.
2016-2017FELLOWS
MedicalCenterandaHematology/OncologyFellowshipattheFoxChaseCancerCenter/TempleUniversityHospital.Hisresearchhasprimarilyfocusedonepigene@ctherapyinMDS/AMLandtheevalua@onofminimalresidualdiseaseinvarioushematologicmalignancies.Throughhispar@cipa@onintheAmericanSocietyofHematologyClinicalResearchTrainingIns@tute(ASH-CRTI)programhewasdevelopedaPhaseIB/IItrialatFoxChaseofanovelepigene@cdrugcombina@ontherapyforelderlyorunfitMDS/AMLpa@ents.
includingorganizingPolioImmuniza@onDriveandBlooddona@on.HefinishedhisInternalMedicineresidenttrainingatWayneStateUniversity,Detroit.Heisinterestedinpursuingacareerfocusonhematologicmalignancyincludingmyeloma,MDSandCML.
NasheedHossain,MD
receivedhismedicaldegreefromtheCaseWesternReserveUniversity.HecompletedhisInternalMedicineresidencyattheUniversityofChicago
AmandeepGodara,MD
finishedhismedicalschoolatGovernmentMedicalCollegeatMaharashtra,India.Duringhismedicalschoolyears,hewasveryac@veinvolunteerworks
SaurabhDahiya,MD
finishedhismedicalschoolatMaulanaAzadMedicalCollegepriortocomingtotheU.S.HecompletedhisInternalMedicineresidencyandHematology/
OncologyfellowshipatBaystateMedicalCenter/Tu?sUniversityinMassachusegs.Hehasbeenveryprolifera@veinpublica@onsincludingmanyfirst-authoredpaperscoveringtopicsfromspontaneouscoronaryarterydissec@ontolymphoma.Hisinterestsoutsideofmedicinearetraveling,exploringvariouscuisinesandamateurwri@ng.
KathrynCappell,MD,PhD
didherundergraduateatUniversityofMiami(asaninspiringmarinebiologist!).However,medicinecharmedherintotheMD/PhDprogram
atUniversityofNorthCarolina-ChapelHill.HerPhDwork(Pharmacology)focusedonfindingwaystoincreasecancercells’sensi@vitytopaclitaxelchemotherapyusingasynthe@clethalscreeningsystem.ShethendidherInternalMedicineresidencyatStanford.Sheisveryinterestedinhematologyandwantstoseekanacademiccareerinthisfield.
STANFORDBMTFALL20167
BMT BLOOD & MARROW TRANSPLANTATION
300 Pasteur Drive Room H0101, MC5623 Stanford, CA 94305
CancerIns@tutealongwiththesupportofStanfordHospital,theStanfordBMTprogramhasbuiltanewexpandedCellularTherapeu@csFacility.Withthisnewfacility,theStanfordBMTprogramwilldeveloplife-savingtreatmentsandimplementnovelclinicaltrialsmoreefficientlyinthecomingyears.
PrecisionMedicinewithTechnologiesTheBMTImmuno-monitoringprogramwillcon@nuetoapplystate-of-arttechnologiessuchasHigh-ThroughputSequencing(HTS),andMassCytometry(CyTOF)tomonitortheminimalresidualdiseaseandthechangesofimmunesystemintransplantpa@ents.
DevelopingNovelCellularTherapeu+csJustlikememoryCD8+Tcells,wewilldevelopnewcellulartherapeu@csusingdifferentcellpopula@ons.ExamplesincludeusingregulatoryTcells(Treg)totreatGVHD;u@liza@onofvirus-
specificcytotoxicTcellsinmanaginglife-threaten-ingviralinfec@ons;engineeringChimericAn@genReceptor(CAR)Tcellstotargetdifferenthematologicalmalignanciesandsolidorgancancer.
ExpandingCellularTherapeu+cstoOtherDiseasesWewillapplynovelapproachestotreatpa@entswithnon-malignantcondi@ons,suchastheongoingtrialwithpurifiedstemcellsinimmuno-deficientpa@ents.Wewillalsousecellulartherapeu@cstomodulatetheimmunesystem,formanagingdiseasessuchasautoimmunediseaseandsolidorgantransplanta@on.
HowYouCanHelpPar@cipa@nginoneofourclinicalstudiesisoneofthemostpreciousgi?sourpa@entscangive.Asareferringphysician,encouragingyourpa@entstoworkwithourteamwouldbeatremendousbenefit.Inaddi@on,ifyouorsomeoneyouknowwouldliketomakeaphilanthropicdona@ontotheBMT,pleasecontactMicheleThompsonat650-725-1109orvisitourwebsite:hgp://bmt.stanford.edu.
ByworkingwithfacultyinotherdivisionswithintheSchoolofMedicineandStanford
CLINICALTRIALHIGHLIGHTSPosttransplantinfusionofallogeneicCD8memoryTcellsasconsolida@ontherapya?ernon-myeloabla@veallogeneichematopoie@ccelltransplanta@oninpa@entswithleukemiaandlymphoma(RobertLowsky,MD)
PhaseI/IItrialforpa@entsundergoingmyeloabla@veallogeneicHCTwithaTcelldepletedgra?withsimultaneousinfusionofconven+onalTcellsandregulatoryTcells(EvereRMeyer,MD,PhD)
Amul@-center,phaseIII,randomizedtrialofreducedintensitycondi@oningandtransplanta@onofdoubleunrelatedumbilicalcoredbloodversusHLA-haploiden+calrelatedbonemarrow(AndrewRezvani,MD)
Arandomized,mul@-center,phaseIIItrialofcalcineurininhibitor-freeinterven+onsforpreven@onofgra?-versus-hostdisease(LoriMuffly,MD,MS)
OURVISION
