抗独特型抗体免疫治疗卵巢癌的动物实验研究

TheStudyofImmunotherapyofOvarianCarcinomawithAnti┐idiotypicAntibody

目的：研究抗独特型抗体对卵巢癌的免疫治疗作用，为临床试验提供动物实验依据。方法：用人卵巢癌抗独特型抗体（Ａｂ２）免疫杂交一代小鼠ＢＣＦ１，为实验组；用正常小鼠ＩｇＧ免疫小鼠ＢＣＦ１，为对照组。两组均免疫３次，于末次免疫后１周，将经裸鼠传代的人卵巢癌细胞系移植于ＢＣＦ１小鼠肾脏包膜下，分别于移植后第２、４、６、８和１０天处死小鼠，取血清进行抗独特型抗体（Ａｂ３）分析。移植瘤行组织学检查，观察宿主淋巴细胞浸润情况及瘤细胞可见率。结果：实验组小鼠肾脏包膜下人卵巢癌细胞系很快受到排斥，在移植后第６天，淋巴细胞浸润即达高峰，而对照组在第１０天才达高峰；瘤细胞可见率，在移植第６天后即明显降低，而对照组呈逐渐下降。结论：Ａｂ２作为抗原免疫小鼠后，能够排斥瘤细胞的生长。

Objectives:Tostudytheroleofanti-idiotypicantibodyinimmunotherapyofovariancarcinoma,andtoinvestigatetheefectofanti-idiotypicantibody(Ab2)onovariancarcinomainvivo.Methods:Sixtoeightweek-oldfemaleBCF1micewereimmunizedthreetimesat28daysintervalswith50～100μgofanti-idiotypicantibodyAb2ofovariancarcinoma.TheinitialimmunizationwasgivenwithcompleteFreund′sadjuvant(CFA),folowedbyincompleteFreund′sadjuvant(IFA).ThecontrolmicewereimmunizedwithnormalmouseIgG.Theovariancarcinomacels(SKOV3)passagedfromnudemiceweretransplantedtothesubrenalcapsulesofimmunizedBCF1miceafterthelastinjection.Thenthemicewerebredseparatelyonthe2nd,4th,6th,8thand10thdaysafterthetransplantationoperations.Specificanti-Ab2(Ab3)inserawasdetectedbyusinginhibitionassayofenzyme-linkedimmunospecificassay.Tumorinfilitrationlymphocytes(TIL)andtumorcelsfromthetumortissueofBCF1wereobservedmicroscopicaly.Results:TheseralevelsofAb3inAb2im-munizedmicewerehigherthanthoseofthecontrols.TILintheformerwerefoundtoreachtheirhighestpeakonthe6thday,whereasthehighestpeakforthecontrolswasonthe8～10thdays;tu-morcelviabilityrateintheformerdecreasedrapidlyafter6days,butinthecontrolsdecreasedonlygradualy.Conclusions:Ab2couldinducespecificimmunorejectiontoovariancarcinomainvivo.Itispredictedthatanti-idiotypicantibodyAb2mightbeusedinimmunotherapyofovariancancerpatientsandalsoasapreventiveforposttreatmentclinicalrecurrenceofovariancarcinoma.