An In Situ Autologous Tumor Vaccination with Combined Radiation Therapy and TLR9 Agonist Therapy 英文参考文献.docVIP

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An In Situ Autologous Tumor Vaccination with Combined Radiation Therapy and TLR9 Agonist Therapy 英文参考文献.doc

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An In Situ Autologous Tumor Vaccination with Combined Radiation Therapy and TLR9 Agonist Therapy 英文参考文献

AnInSituAutologousTumorVaccinationwithCombined RadiationTherapyandTLR9AgonistTherapy HuagangZhang1,LaibinLiu1,DongYu4,EkambarR.Kandimalla4,HuiBinSun1,2,SudhirAgrawal4, ChandanGuha1,3 * 1DepartmentofRadiationOncology,AlbertEinsteinCollegeofMedicineandMontefioreMedicalCenter,Bronx,NewYork,UnitedStatesofAmerica,2Departmentof Orthopedics,AlbertEinsteinCollegeofMedicineandMontefioreMedicalCenter,Bronx,NewYork,UnitedStatesofAmerica,3DepartmentofPathology,AlbertEinstein CollegeofMedicineandMontefioreMedicalCenter,Bronx,NewYork,UnitedStatesofAmerica,4IderaPharmaceuticals,Inc.,Cambridge,Massachusetts,UnitedStatesof America Abstract Purpose:RecentstudieshaveshownthatanewgenerationofsyntheticagonistofToll-likereceptor(TLR)9consistinga39- 39-attachedstructureandadCp7-deaza-dGdinucultodieshowsmorepotentimmunostimulatoryeffectsinbothmouseand human than conventional CpG oligonucleotides. Radiation therapy (RT) provides a source of tumor antigens that are releasedfromdying,irradiated,tumorcellswithoutcausingsystemicimmunosuppression.We,therefore,examinedeffect ofcombiningRTwithadesignersyntheticagonistofTLR9onanti-tumoralimmunity,primarytumorgrowthretardationand metastasesinamurinemodeloflungcancer. Methods:GroupedC57BL/6andcongenicBcelldeficientmice(B2/2)bearingfootpad3LLtumorsweretreatedwithPBS, TLR9agonist,controloligonucelotide,RTorthecombinationofRTandTLR9agonist.Immunephenotypeofsplenocytes andserumIFN-candIL-10levelswereanalyzedbyFACSandELISA,24haftertreatment.Tumorgrowth,lungmetastases andsurvivalrateweremonitoredandtumorspecificantibodiesinserumanddepositionintumortissueweremeasuredby ELISAandimmunofluorescence. Results:TLR9agonistexpandedandactivatedBcellsandplasmacytoiddendriticcellsinwild-typemiceandnaturalkiller DCs (NKDCs) in B cell-deficient (B2/2) mice bearing ectopic Lewis lung adenocarcinoma (3LL). Combined RT with TLR9 agonisttreatmentinhibited3LLtumorgrowthinbothwildtypeandB2/2mice.Astrongtumor-specifichumoralimmune response(titer:1/3200)withdepositionofmouseI