熊本大学学術リポジトリ Kumamoto University Repository System
熊本大学学術リポジトリ Kumamoto University Repository System
熊本大学学術リポジトリ Kumamoto University Repository System
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SummaIy<br />
Purpose:Tbestablishcffcctivcdiagnosticmcthodandanti-tumorimmunotherapyfOrseveral<br />
canccrs,wctricdtoidcntifyanoveltumor色associatcdantigcn.<br />
Experimentaldesign:WCanalyzcddataobtaincdfromcDNAmicroarrayanalysisofdiffUsc<br />
gastriccanccrtissueand29normaltissucstofindanovcltumor迄associatcdantigen,secretcd<br />
protcinacidicandrichinCystcinc(SPARC).Becausemclanomaccllswcrcreportedto<br />
cxpressalargcamountofSPARC,andbccauseSPARCisasccrctcdprotein,atfi応t,sccrcted<br />
SPARCproteinwasquantificdusingELISAinthcscrafromlO9mclanomapaticnts,s<br />
paticntswithlargccongenitalmclanocyticnevus,61age-matchcdhealthydonorsandl3<br />
discasc-frccpatientsaftcrundcrgoingasurgicalrcmovaLWCalsoquantificdtwoothcrknown<br />
tumormarkcrsfOrmclanoma,GPC3and5-S-cystcinyldopa(5-S-CD),inthcsamcscrum<br />
samplcs,andcomparcdthcscmarkcrsfOrthcirdiagnosticvaluc・Bccauscofthcsimilariticsin<br />
thcbindingpeptidcmotifSsharcdbetwccnH2-KdandHLA-AZ4(A*2ｲ02),4pcptidcshaving<br />
thcsemotifSwcrcsynthesizedThcn,wcinvestigatedwhcthcrthcH2-Kd-restrictedSEARC<br />
pcptidcscouldinduccSPARCrcactivecytotoxicT1ymphocytcs(CTLs)ornot・Inaddition,<br />
wcinvcstigatcdtheeffCctofthcprc-immunizationofBM-DCpulsedwiththcSEARCcpitopc<br />
pcptidcsonagrowthofSPARC-cxprcssingtumorccllsimplantcdinBALB/Cmousc.<br />
ResuuIts:In20diffUscgastriccanccrtissucs,anavcragcofrclativcratioofthccxprcssionof<br />
thcSPARCmRNAincancercellsversusadjaccntnormalgastricmucosaswasl33,359.RIz<br />
PCR,wcstcmblottingandimmunohistochemicalanalysisrcvcalcdthat,SPARCis<br />
overcxpresscdinmelanoma・ThcscrumSPARCconccntrationsinmelanomapatientswcrc<br />
grcatcrthanthoscinhcalthydonors(P=0.001)Whcnwcfixedacutoffvalucatthcmcan<br />
conccntrationplus2SDofthehcalthydonors,thcscmmSRARCwasfOundtobcincreasedin<br />
thcseraof36(33%)ofthelO9melanomapaticnts,whcrcasthcrewcrc3(49%)falscpositivccasesoutof61hcalthydonors・Sumrisingly,19of36paticntsshowingincrcascd<br />
SPARClcvclswercinstagcsO-ILThcscrumSPARC1cvcldccreasedunderthccutofflcvclin<br />
lOofl3paticntsaftcrsurgicalrcmovaLUsingSPARCandGPC3incombinationcnabledus<br />
todctcct47of75(66.2%)mclanomapaticntsatancarlystage(0-11).SPARCprotcincontains<br />
ZcpitopcsrccogmzcdbymouscH2-Kd-rcstrictcdCTLsThcscCTLs,gcncratedinBALB/C<br />
mousc,hadcytotoxicactivityagainstcancercelllincspositivcfOrSPARC・Furthcnnorc,prc‐<br />
immunizationofBALB/CmicewithBM-DCpulscdwiththcSPARCepitopcpcptidcs<br />
prcvcntedthcgrowthofthcmouscfibrosalcomacclllinc(McthA)engraftcdinBALB/c<br />
mouscandcontributcdtoclongationofsurvivaltimcwithoutcausingautoimmuncdiscascs.<br />
Conclmsions:SEARCmayprovctobcanidealtumor上associatcdantigcnuscfUlfOrdiagnosis<br />
andimmunotherapyofcancersincludingmclanoma・cDNAmicroarrayanalysisisausefill<br />
mcthodtoidcntifytumoﾄassociatedantigensuscfUlfOrcanccrdiagnosisandimmunothcrapy.<br />
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