Enhancement of anti-murine colon cancer immunity by fusion of a SARS fragment to a low-immunogenic carcinoembryonic antigen.docVIP

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Enhancement of anti-murine colon cancer immunity by fusion of a SARS fragment to a low-immunogenic carcinoembryonic antigen.doc

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Enhancement of anti-murine colon cancer immunity by fusion of a SARS fragment to a low-immunogenic carcinoembryonic antigen

Linetal.BiologicalProceduresOnline2012,14:2 /content/14/1/2 Biological Procedures Online RESEARCH OpenAccess Enhancementofanti-murinecoloncancer immunitybyfusionofaSARSfragmenttoa low-immunogeniccarcinoembryonicantigen Chen-SiLin1,Shih-HanKao2,Yu-ChengChen2,Chi-HanLi2,Yuan-TingHsieh2,Shang-ChihYang2,Chang-JerWu3, Ru-PingLee4andKuang-WenLiao2* Abstract Background:Itiswidelyunderstoodthattumorcellsexpresstumor-associatedantigens(TAAs),ofwhichmanyare usuallyinlowimmunogenicity;forexample,carcinoembryonicantigen(CEA)isspecificallyexpressedonhuman coloncancercellsandisviewedasalow-immunogenicTAA.HowtoactivatehostimmunityagainstspecificTAAs andtosuppresstumorgrowththereforebecomesimportantincancertherapydevelopment. Results:ToenhancetheimmuneefficiencyofCEAinmicethatreceived,wefusedapartialCEAgenewith exogenousSARS-CoVfragments.OralvaccinationofanattenuatedSalmonellatyphimuriumstraintransformedwith plasmidsencodingCEA-SARS-CoVfusiongeneintoBALB/cmiceelicitedsignificantincreasesinTNF-aandIL-10in theserum.Inaddition,asmallertumorvolumewasobservedinCT26/CEA-bearingmicewhoreceivedCEA-SARS- CoVgenetherapyincomparisonwiththoseadministeredCEAalone. Conclusion:TheadministrationoffusingCEA-SARS-CoVfragmentsmayprovideapromisingstrategyfor strengtheningtheanti-tumorefficacyagainstlow-immunogenicendogenoustumorantigens. Keywords:immunotherapy,tumor-derivedpeptide,tumorvaccine,low-immunogenicity Background and vaccination with CEA has been demonstrated to Tumor-associatedantigens(TAAs)areattractivecandi- induce,althoughwithonlyminoreffects,bothhumoral dates for cancer therapy in view of their specificity to andT-cellresponses[3].InordertomagnifytheCEA- tumortargets andsafety profile. Althoughmostknown mediatedtumor-specificimmuneactivities,co-adminis- tumor antigens can generate cancer-specific immune tration ofCEAwithotherimmune-response enhancers responses,theyareeitherpoorlyimmunogenicorfunc- suchasgranulocyte-macrophagecolony-stimulatingfac- tionally non-immunogenic,