异种黑色素瘤抗原不同途径注射诱发的肿瘤免疫及自免疫的比较  

Comparison of tumor immunity and autoimmunity induced by Adtrp2 in different injection route

作　　者：刘红菊[1] 熊先智[1] 张玉[2] 李卓亚[3] 

机构地区：[1]华中科技大学同济医学院附属协和医院呼吸内科 [2]华中科技大学同济医学院附属协和医院药剂科 [3]同济医学院免疫学系,湖北武汉430022

出　　处：《中国医院药学杂志》2009年第20期1715-1718,共4页Chinese Journal of Hospital Pharmacy

基　　金：回国留学人员启动基金(编号:20071108)

摘　　要：目的:为取得较佳的肿瘤免疫而伴随较小的自免疫损伤的途径,比较了接种腺病毒载体(Ad)介导人黑色素瘤相关抗原酪氨酸酶相关蛋白2(Trp2)时的不同途径与其效果的关系。方法:使用Ad编码的人Trp2(Ad hTrp2)分别不同途径(皮内id、肌注im和静脉注射iv)注射免疫C57BL/6小鼠(分为id组i、m组和iv组),每组给予不同免疫剂量(105,106,107,108,每组剂量10只小鼠),2周后,用体内细胞毒性T淋巴细胞(CTL)杀伤试验分析CTL杀伤活性及其量效关系。并于id和im时比较多次与单次的免疫效应,观察免疫2周鼠(每组剂量10只小鼠)皮下接种105B16F10黑色素瘤细胞后的肿瘤保护及白癜风形成情况,持续3个月。结果:(1)3种注射途径中,Ad hTrp2诱发小鼠CTL杀伤活性与其免疫剂量呈明确的量效关系,其中,im和id注射活性较iv强烈。(2)im和id注射时,重复与单次的疫苗免疫效果无明显差异。(3)Ad hTrp2免疫小鼠,其肿瘤保护作用于3个月的观察中持续存在。(4)而局部白癜风形成只在Ad hTrp2id组发现,于Ad hTrp2im未发现白癜风。这说明:Ad介导异种基因hTrp2的单次免疫即有效地克服了自身mTRP2的免疫耐受,诱发了强烈的抗原特异性细胞免疫反应。同时,通过im的免疫途径,诱发了较强的抗肿瘤免疫效果,可有效克服自身免疫损伤。结论:自身免疫损伤并不是一定伴随较强的抗肿瘤免疫而出现。OBJECTIVE To find an effective method to balance tumor immunity and autoimmunity. METHODS C57BL/6 mice were immunized with AdhTrl〉2 by intracutaneous, intramuscular and intravenous route with different AdhTrp-2 dose of 10^5,10^6,10^7 and 10^8 separately in each group（ 10 mice in each group）. Two weeks after immunization, in vivo CTL assay was analysed to understand the immunized relationship between dose and effect. Tumor growth and vitiligo were observed until 3 months after 10^5 B16F10 tumor challenge and the above protection of single immune was compared with repeated immune in intracutaneous or intramuscular injection. RESULTS （1）CTL activity was proportional to immunie dose activity of iv injection and was weaker than hat of im or id injection. （2）Through im or id immunization, there was no significant difference between single injection and repeated injection. （3） The protection against melanoma induced by AdhTrp2 immuization lasted at least 3 months. （4）Vitiligo was observed in all mice immunized with AdhTrp2 only in injection intracutaneously not intramuscularly. CONCLUSION It shows that anti-melanoma response by genetic vaccination-expressing xenoantigens is feasible.

关 键 词：腺病毒 抗原 肿瘤免疫 自身免疫 

分 类 号：R969[医药卫生—药理学]