CD40-Activated B Cell Cancer Vaccine Improves Second Clinical Remission and Survival in Privately Owned Dogs with Non-Hodgkins Lymphoma 英文参考文献.docVIP

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CD40-Activated B Cell Cancer Vaccine Improves Second Clinical Remission and Survival in Privately Owned Dogs with Non-Hodgkins Lymphoma 英文参考文献.doc

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CD40-ActivatedBCellCancerVaccineImprovesSecond ClinicalRemissionandSurvivalinPrivatelyOwnedDogs withNon-Hodgkin’sLymphoma KarinU.Sorenmo1*.,ErikaKrick1,ChristinaM.Coughlin3,BethOverley1,ThomasP.Gregor1,RobertH. Vonderheide3,4*.,NicolaJ.Mason 1,2,4 . * 1DepartmentofClinicalStudies,UniversityofPennsylvania,Philadelphia,Pennsylvania,UnitedStatesofAmerica,2DepartmentofPathobiology,SchoolofVeterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 3Department of Medicine, School of Medicine, Abramson Family Cancer ResearchInstitute,UniversityofPennsylvania,Philadelphia,Pennsylvania,UnitedStatesofAmerica,4AbramsonCancerCenter,UniversityofPennsylvania,Philadelphia, Pennsylvania,UnitedStatesofAmerica Abstract Cell-basedactiveimmunotherapyforcancerisapromisingnovelstrategy,withthefirstdendriticcell(DC)vaccineachieving regulatoryapprovalforclinicaluselastyear.Manufacturingremainsarduous,especiallyforDCvaccines,andtheprospectof usingcell-basedimmunotherapyintheadjuvantsettingorincombinationwithchemotherapyremainslargelyuntested. Here, we used a comparative oncology approach to test the safety and potential efficacy of tumor RNA-loaded, CD40- activatedBcellsinprivatelyowneddogspresentingwithnon-Hodgkin’slymphoma(NHL),aclinicalscenariothatrepresents notonlyamajorprobleminveterinarymedicinebutalsoabonafidespontaneousanimalmodelforthehumancondition. When administered to NHL dogs in remission after induction chemotherapy, CD40-B cells electroporated ex vivo with autologous tumor RNA safely stimulated immunity in vivo. Although chemotherapy plus CD40-B vaccination did not improve time-to-progression or lymphoma-specific survival compared to dogs treated with chemotherapy alone, vaccination potentiated the effects of salvage therapy and improved the rate of durable second remissions as well as subsequent lymphoma-specific survival following salvage therapy. Several of these relapsed dogs are now long-term survivorsandfreeofdiseaseformo