Effective Melanoma Immunotherapy in Mice by the Skin-Depigmenting Agent Monobenzone and the Adjuvants Imiquimod and CpG 英文参考文献.docVIP

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Effective Melanoma Immunotherapy in Mice by the Skin-Depigmenting Agent Monobenzone and the Adjuvants Imiquimod and CpG 英文参考文献.doc

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Effective Melanoma Immunotherapy in Mice by the Skin-Depigmenting Agent Monobenzone and the Adjuvants Imiquimod and CpG 英文参考文献

EffectiveMelanomaImmunotherapyinMicebytheSkin- DepigmentingAgentMonobenzoneandtheAdjuvants ImiquimodandCpG JasperG.vandenBoorn1,DebbyKonijnenberg1,EstherP.M.Tjin1,DaisyI.Picavet1,NicoJ. Meeuwenoord2,DmitriV.Filippov2,J.P.WietzevanderVeen1,4,JanD.Bos1,CornelisJ.M.Melief3, RosalieM.Luiten1* 1DepartmentofDermatologyandtheNetherlandsInstituteforPigmentDisorders,AcademicMedicalCenter,UniversityofAmsterdam,Amsterdam,TheNetherlands, 2Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands, 3Department of Immunohematology and Blood Transfusion, Leiden University Medical Center,Leiden,TheNetherlands,4DepartmentofDermatology,NetherlandsCancerInstitute–AntonivanLeeuwenhoekHospital,Amsterdam,TheNetherlands Abstract Background: Presently melanoma still lacks adequate treatment options for metastatic disease. While melanoma is exceptionally challenging to standard regimens, it is suited for treatment with immunotherapy based on its immunogenicity.Sincetreatment-relatedskindepigmentationisconsideredafavourableprognosticsignduringmelanoma intervention,wehereaimedatthereverseapproachofdirectlyinducingvitiligoasashortcuttoeffectiveanti-melanoma immunity. MethodologyandPrincipalFindings:Wedevelopedaneffectiveandsimpletouseformofimmunotherapybycombining the topical skin-bleaching agent monobenzone with immune-stimulatory imiquimod cream and cytosine-guanine oligodeoxynucleotides(CpG)injections(MICtherapy).Thispowerfulnewapproachpromptlyinducedamelanomaantigen- specific immune response, which abolished subcutaneous B16.F10 melanoma growth in up to 85% of C57BL/6 mice. Importantly,thisregimeninducedover100daysoftumor-freesurvivalinupto60%ofthemice,andforcefullysuppressed tumorgrowthuponre-challengeeither65-or165daysafterMICtreatmentcessation. Conclusions: MIC therapy is effective in eradicating melanoma, by vigilantly incorporating NK-, B- and T cells in its therapeutic effect. Based on these results, the MIC regimen presents a high-yield, low-cost and simple ther