what is cancer immunotherapy?€¦ · what is cancer immunotherapy? cancer immunotherapy is one of...
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1 Letterman Drive, D3500, San Francisco, CA 94129 I (415) 985-7311 I www.parkerici.org
WHATISCANCERIMMUNOTHERAPY?
Cancerimmunotherapyisoneofthemostimportantmedicaladvancesofourtime,andthefirstapproachwiththepotentialtogeneratelong-lastingregressionsforalltypesandstagesofcancer.Itharnessesthebody’sownpowerfulimmunesystemandmobilizesitshighlyrefineddisease-fightingarsenaltoeliminatecancercells.Theimmunesystemproducesspecializeddisease-fightingcellsthatcirculatethroughoutthebody,continuallyseekingoutanddestroying“foreign”agents.Thesimilaritybetweencancercellsandhealthytissuesblindfoldstheimmunesystem,whichallowscancertoeludedetection.Cancerimmunotherapiesoverwhelmcancer’sevasivestrategies,toensurethatapowerful,preciseandadaptableimmuneattackisfocusedontumorsanywhereinthebody.
Ithasmanyadvantagesoverprevioustypesofcancertreatments:
• Precise:Immunotherapyhasthepotentialtokillcancercellswithoutharminghealthytissue.
• Systemic:Theimmunesystemcanhomeinoncancerandattacktumorsanywhereinthebody.
• Dynamic:Astumorsevolve,theimmunesystemadaptsintandem,sustainingprotectionfromcancer.
• Powerful:Theimmunesystemcansuccessfullyeliminateevenlargeandadvancedtumors.
• Durable:Immunecells“remember”cancercellstokeepthemfromcomingback.• Universal:Immunesystem-basedtreatmentshavethepotentialtobeeffectivefor
virtuallyallformsofcancer.• Synergistic:Immunotherapycanenhanceandcomplementtheeffectivenessof
conventionalcancertherapies.• Curative:Patientstreatedwithimmunotherapieshaveachievedcomplete,long-lasting
remissionsofcancersthatuntilrecentlywereconsidereduntreatable.
WHYNOW?
Weareataninflectionpoint.Thecancerimmunotherapyfieldhasmadetremendousprogressinjustafewshortyears,muchofitspearheadedbyParkerInstitutescientists.Wenowhaveabetterabilitytostudycanceranditsresponsetotreatmentatthemolecularlevel,togeneticallyengineercellsastherapies,andhaveagreaterunderstandingoftheroleoftheimmunesystem.Inthe1990s,ParkerInstitutescientistsJimAllison,PhD,andJeffBluestone,PhD,independentlydiscoveredthat,topreventautoimmunityandoverreactions,amoleculecalledCTLA-4actsasa“brake”orcheckpoint,ontheimmuneresponse.Thisinsightledtothedevelopmentofdrugscalled“checkpointinhibitors.”First-generationcheckpointinhibitordrugshaveachievedunprecedentedresponsesinmelanoma,lungandkidneycancers,andarebeingdevelopedforvirtuallyeveryothertypeoftumor.
1 Letterman Drive, D3500, San Francisco, CA 94129 I (415) 985-7311 I www.parkerici.org
Inseparatestudies,thedevelopmentofcancer-targetingT-celltherapies(termedCAR-Ts),pioneeredbyCarlJune,MD,andothers,hasledtoimpressiveresultsinseveralbloodcancersinchildrenandadults.
ThesebreakthroughshaveresultedinindustryrecognitionandrecentFDAapprovals,furtheracceleratingthefield’sprogress.Thereisnowawidespreadconsensusthattheimmunesystemisapromisingmechanismtotreatcancer.ImmunotherapywasSciencemagazine’s2013“BreakthroughoftheYear,”andtheAmericanSocietyofClinicalOncology(ASCO)followedin2016,namingcancerimmunotherapyitsadvanceoftheyear.
WithrecentscientificdiscoveriesandtheParkerInstitute’spioneeringorganizationalmodel,weexpecttodramaticallyaccelerateresearchbreakthroughsandhastenthedeliveryofbettertreatmentstopatients.
WHATWILLTHEPARKERINSTITUTE’SRESEARCHFOCUSON?
TheParkerInstitute’sresearcheffortswillspantheentirefieldofcancerimmunology,buttheteamwillinitiallymakebigbetsonthreemajorcross-cuttingcollaborativeresearchprojects:
• Best-in-classT-cells:Incell-basedtherapiesknownasCAR-T(ChimericAntigenReceptorT-cell)orTCR(T-cellReceptor)therapy,theimmunesystem’smainanti-cancerwarriors,T-cells,areharvestedfromapatient’sbloodandgeneticallyengineeredtotargetproteinsorpeptidesthatareabundantinthepatient’stumor.Billionsofthesemodifiedcellsarereturnedtothepatient’sbloodstream,wherethecellsseekoutandattacktumors.ParkerInstitutescientistCarlJune,MD,pioneeredCAR-Ttherapyforacutelymphoidleukemia(ALL),whichhasbeenenormouslysuccessful:over90percentofALLpatientsreceivingCAR-Ttherapyachievedcompleteremission.TheParkerInstitutewilldeveloplaboratoryandclinicalstudiesthataimtoidentifythepathwaysandfactorsthatmodulateT-cellactivityandsurvival,anddevelopanewgenerationofmoreeffectiveT-celltherapies.
• CheckpointBlockadeNon-ResponderBiomarkers&Therapeutics:“Checkpointinhibitor”drugs“releasethebreaks”thattheimmunesystemhasinplacetopreventoverreactions,sotheimmunesystemcanattackcancers.First-generationdrugsthattargetCTLA-4andanothercheckpointmoleculecalledPD-1haveachievedunprecedentedresponsesinmelanoma,lung,andkidneycancers,andarebeingdevelopedforvirtuallyeveryothertypeoftumor.TheParkerInstituteteamwillresearchnovelpathwaysandsynergisticcombinationtreatmentstoimprovepatientresponseratesandexpandthetreatmenttomoretypesofcancer.
• TumorAntigenDiscovery:Immune-boostingdrugsincludevaccines,therapeuticviruses,andsubstancesdesignedtostimulatetheimmunesystemtorecognizeandmorepotentlyattackapatient’stumors.TheParkerInstituteteamwilluseadvancedDNAsequencing,antigenicpeptidediscoveryeffortsandimmunemonitoring
1 Letterman Drive, D3500, San Francisco, CA 94129 I (415) 985-7311 I www.parkerici.org
technologiestoidentifyselfandmutatedproteinsasnovelantigensfortumortargeting,andthendevelopvaccinesandCAR/TCRtherapiesagainstthesetargets.Thiscouldimprovetheeffectivenessandbroadentheapplicabilityofvaccinesandcellulartherapiestomanyadditionaltypesofcancer.
FASTFACTS
• Eachyear,14millionpeoplearediagnosedwithcancerand8.2millionpeopledieofcancer-relatedcauses.
• Therearewellover1,500cancerimmunotherapydrugscurrentlyintheresearchanddevelopmentpipeline,thesecondlargestareaofalldrugdevelopment.
HOWDOESIMMUNOTHERAPYWORK?