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1、HarnessingSolubleNKCellKillerReceptorsfortheGenerationofNovelCancerImmuneTherapy1234335TalI.Arnon,GalMarkel,AhuvaBar-Ilan,JacobHanna,EyalFima,FabriceBenchetrit,RuthGalili,6773.5.AdelheidCerwenka,DanielBenharroch,NettaSion-Vardy,AngelPorgador*,OferMandelboim*1Division
2、ofBiology,CaliforniaInstituteofTechnology,Pasadena,California,UnitedStatesofAmerica,2ShebaCancerResearchCenter,ShebaMedicalCenter,TelHashomer,Israel,3TheShragaSegalDepartmentofMicrobiologyandImmunologyandtheNationalInstituteforBiotechnologyintheNegev,BenGurionUnivers
3、ityoftheNegev,BeerSheva,Israel,4TheWhiteheadInstituteforBiomedicalResearch,Cambridge,Massachusetts,UnitedStatesofAmerica,5LautenbergCenterforGeneralandTumorImmunology,TheHebrewUniversityHadassahMedicalSchool,Jerusalem,Israel,6DivisionofInnateImmunity,GermanCancerRese
4、archCenter,Heidelberg,Germany,7ThePathologyDepartment,SorokaHospital,BeerSheva,IsraelAbstractThenaturalcytotoxicreceptors(NCRs)areauniquesetofactivatingproteinsexpressedmainlyonthesurfaceofnaturalkiller(NK)cells.TheNCRs,whichincludethreemembers;NKp46,NKp44andNKp30,ar
5、ecriticallyinvolvedinNKcytotoxicityagainstdifferenttargets,includingawiderangeoftumorcellsderivedfromvariousorigins.EventhoughthetumorligandsoftheNCRshavenotbeenidentifiedyet,theselectivemannerbywhichthesereceptorstargettumorcellsmayprovideanexcellentbasisforthedevel
6、opmentofnovelanti-tumortherapies.TotestthepotentialuseoftheNCRsasanti-tumoragents,wegeneratedsolubleNCR-IgfusionproteinsinwhichtheconstantregionofhumanIgG1wasfusedtotheextracellularportionofthereceptor.Wedemonstrate,usingtwodifferenthumanprostatecancercelllines,thatt
7、reatmentwithNKp30-Ig,dramaticallyinhibitstumorgrowthinvivo.ActivatedmacrophageswereshowntomediateanADCCresponseagainsttheNKp30-Igcoatedprostatecelllines.Finally,theIgfusionproteinswerealsodemonstratedtodiscriminatebetweenbenignprostatehyperplasiaandprostatecancer.Thi
8、smayprovideanoveldiagnosticmodalityinthedifficulttaskofdifferentiatingbetweenthesehighlycommonpathologicalconditions.Citation:Arnon
