重组腺病毒人体恶性肿瘤内注射体内外播散性研究  

RESEARCH ON DISSEMINATION OF RECOMBINANT ADENOVIRUS INTRA-TUMOR INJECTION IN HUMAN BODY

作　　者：陆巍[1] 陆维祺 朱隽[1] 郑树[2] 

机构地区：[1]复旦大学附属中山医院普外科,上海200032 [2]浙江大学肿瘤研究所

出　　处：《现代预防医学》2007年第3期403-404,415,共3页Modern Preventive Medicine

基　　金：国家"863"高科技项目(2002AA2Z3304)

摘　　要：[目的]E1b缺失的重组腺病毒因其能在肿瘤细胞中特异复制,是目前较有希望的生物治疗方法之一,但是其体内应用仍需慎重。本研究主要通过观察重组腺病毒人体体表恶性肿瘤内注射后体内外播散状况并推测其在试验期内的环境安全性。[方法]收集参加E1b缺失的重组腺病毒H101临床试验病人的外周血、尿、粪、咽拭子、注射部位皮肤拭子和肿瘤组织活检标本进行相应检测。[结果]聚合酶链反应检测,外周血H101 DNA,d1、5、22阳性率分别为:32.4%、40.6%、5.3%,尿、粪、咽拭子、注射部位皮肤拭子阳性率均为0;治疗前后抗人5型腺病毒抗体阳性率分别是27.5%和61.1%;肿瘤组织腺病毒免疫组织化学检查,阳性6/9例。[结论]发现重组腺病毒H101在肿瘤内复制和体内播散证据,未发现其体外播散证据,重组腺病毒体表肿瘤注射,治疗期内环境安全。[Objective] Elb deleted adenovirus is a promising cancer oncolytic virus therapy which has been developed recently, however, great caution should be paid to in vivo application of replication competent virus. The study aimed to observe the dissemination of recombinant adenouvrus and evaluate its environment safety during experiment session. [Methods] Clinical specimens of patients treated with H101 intra-tumor injection were collected for H101 detection, including blood, urine, stool, pharynx swab, swab of injection place and tumor biopsy. [Results] The clinical specimens were detected for H101 contamination by PCR at day of 1, 5 and 22, the positive rates of DNA in peripheral blood were 32.4% , 40.6% and 5.3% respectively. Serum antibody level of adenovirus type 5 was 27.5% and 61.1% before and after treatment. Adenovirus capsule was found in 6/ 9 patients. [Conclusions] H101 can disseminate in human body but not environment by intra-tumor injection. It is safe to the environment during treatment.

关 键 词：播散 重组腺病毒 环境安全性 

分 类 号：R73-362[医药卫生—肿瘤]