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CancerTherapy•Surgery-�Localizedtumors•Radiation-�Metastastictumors�Affectsproliferatingcells(bonemarrow,etc.)�Radiation-resistanttumorsdevelop•Chemotherapy-�Metastastictumors�Affectsproliferatingcells(bonemarrow,etc.)�Drug-resistanttumorsdevelop•Immunotherapy-�Metastastictumors�Specificity�Donotdevelopresistance�NotoxicityTumorImmunotherapyWhatisImmunotherapy?•Immunotherapy(alsoknownasbiologictherapyorbiotherapy)istreatmentthatusescertainpartsoftheimmunesystemtofightdisease,including:•Immunodeficiency;•Cancer;•Infection;•Autoimmunity;•Hypersensitivity;•Graftrejection;•Inflammatory;ImmuneenchantmentTherapyImmuosuppressionTherapyTumorImmunotherapy•Passiveimmunotherapy•MonoclonalAntibody(mAb)•Activeimmunotherapy•Non-specific(InnateImmunity)•Bacterialmaterial•Cytokine•Specific•Vaccine•ImprovementofVaccineEfficay•AdjuvantPassiveimmunotherapy•Passiveimmunotherapyusesaspecialtypeofantibodywhichisdevelopedoutsideofapatient'sbody.•Thisantibodyprovidesprotectionagainstdiseaseandhelpstofightoffaninfection,orincancertreatmenttoattacktumorcells.•Theyaredesignedtoattackforeignsubstancesdirectly.•Theydonotstimulateaperson'simmunesystemtoplayanactiveroleinfightingtheinfection.•In1890,EmilBehringandShibasaburoKitasatoreportedanextraordinaryexperiment.TheyimmunizedrabbitswithTetanus/Diphtheria(破傷風/白喉)andcollectedserumfromtheseimmuneanimals.•Theyinjected0.2mloftheimmuneserumintotheabdominalcavityofsixmice.After24hours,theyinfectedthetreatedanimalsanduntreatedcontrolmicediedwithin48hrofinfection,thetreatedmicenotonlysurvivedbutshowednoeffectsofinfection.ClinicalfocusClinicalfocus--PassivetherapyPassivetherapyPassivetherapyPassivetherapy•First,itshowedthatfollowingimmunization,substancesappearedinserumthatcouldprotectananimalagainstpathogens•Second,thisworkdemonstratedthatimmunitycouldbepassivelyacquired•Afewyearslater,in1901,vonBehringwasawardedthevonBehringPassiveImmunotherapyAntibodytransfer•Serum(1901)•TotalImmunoglobulin(Totalantibodypurifiedfromserum)(~1940)•Polyclonalantibody(antigen-specific,multipleepitope(抗原決定區域))•Monoclonalantibody(antigen-specific,singleepitope)(抗原決定區域)(~1970)Epitope•Anepitope,alsoknownasantigenicdeterminant,isthepartofanantigenthatisrecognizedbytheimmunesystem,specificallybyantibodies,Bcells,orTcells•Theepitopesofproteinantigensaredividedintotwocategories,(conformationalepitopes;discontinuous)andlinearepitopes;continuous).ProductionofMonoclonalAntibodies為什麼單株抗體(mAb)在臨床上的應用較為普遍,多株抗體有何缺點??MonoclonalAntibodies-Herceptin•Herceptin例如約25%至30%的原發性乳癌病人中有過度HER2表現的現象，這些病人會比腫瘤細胞無過度HER2表現的病人的存活時間短。1998年核准的Herceptin即為一單株抗體，它可選擇性地與HER2結合而抑制此蛋白質的過度表現。臨床實驗顯示可延長病人壽命約九個月AntibodyAntibody--MediatedEffectorsMediatedEffectorsFunctionsFunctions•Antibody-DependentCell-MediatedCytotoxicity(ADCC):Thelinkingofantibodyboundtotargetcells(virusinfectedcellsofthehost)withtheFcreceptors(CD16)cankillthecell.Inthisprocess,calledADCC,theNKcellcausedeathbyapoptosisofthetargetcell.MonoclonalAntibodies-Rituxan•RituxanCD20抗原係一32-kD不含醣鏈之磷蛋白。它幾乎存在於所有B-淋巴球的表面。當初會選擇抗CD20單株抗體來治療復發性低惡性度非何杰金氏淋巴瘤，其原因有二：第一、超過百分之九十之低惡性度非何杰金氏淋巴瘤都是B-細...