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1、Vaccinesforglioblastomaandhigh-gradegliomaChristopherJ.WheelerandKeithL.Black,MaxineDunitzNeurosurgicalInstitute,DepartmentofNeurosurgeryCedars-SinaiMedicalCenter,LosAngeles,CaliforniaExpertRev.Vaccines10(6),875–886(2011)over22,000patientsannuallyintheUSAGBM-----50%ofallprimar
2、ybraintumorsand21%ofallcentralnervoussystemtumorsinadultsSurvivalrepresentsthemostobjectivestandardforevaluatingGBMtherapy15-monthmediansurvival;<28%ofpatientssurviving2years.Cancervaccines,anddendriticcell(DC)vaccinesinparticular,representannovelandemergingapproachtoGBMtherap
3、yreachtheentireCNSvolumeminimallytoxictonormalbrainandshouldlimitorcounteracttreatmentresistance.retaintumordestroyingcapacityoveraprolongedperiodIntroductiontogliomavaccinesTheclinicalefficacy-----controversial.DC-basedvaccinetherapies-----prostatecancer,renalcellcarcinoma,no
4、n-small-celllungcarcinoma,coloncancerandmalignantglioma/GBM.Poorcorrelation-----immunologicalandclinicalmetricsnorationalwaytodesignvaccinesyouth-thestrongestfavorableprognosticfactorformalignantgliomas;impactimmuneefficacyIntroductiontogliomavaccinesTheimprovement--maximizing
5、antitumorpotencyofeffectorimmunecells,counteractinglocalresistanceoftumorstoimmuneeffectoractivityandminimizingpotentiallydetrimentalsideeffects.Todate,mostGBMvaccineshavebeengeneratedusinguncharacterizedautologoustumorlysateastheantigensource.includingnormalbraincomponents,in
6、ducingimmuneresponsestonormalbraincomponentsSideeffectsaftersuchvaccinationtypicallyconsistofmildfever,rashorirritationnearinjectionsites.VaccinecompositionDCs:themostpotent,innateimmuneantigen-presentingcells,uptakeandprocessexogenousantigenforpresentationtobothCD4+(‘helper’)
7、TcellsandCD8+(‘killer’)Tcells;promotenaturalkillerandnaturalkillerTimmunecellactivitycell-freeadjuvants:inflammatorymediators,damagedtissueormicrobialpathogens,andallsuchactivators.DCvaccines---subcutaneouslyorintradermally,inweeklyorbiweeklycourses,interactwithantigen-specifi
8、cTcellsantigen-pulsedimmatureorsemimatureDCs18reportsofclinic
