PHASE I/II STUDY OF VACCINIA-HPV RECOMBINANT

“在大多数的 宫颈癌的病因是人乳头瘤病毒。由于这 病毒产生对宿主来说是外来的致癌蛋白， 应该对免疫系统敏感， 逃避免疫监视HPV 16、18和33型是 与75-90%的宫颈癌有关。E6和E7是 主要的转化蛋白，并需要维持 转化的表型。E6和E7的转化活性 被认为是由于它们对P53和RB的抑制作用， 分别临床前研究表明， 表达E7和E6的非致瘤性转染子可以保护 小鼠从随后的攻击与肿瘤表达这些 proteins.活的重组痘苗病毒HPV构建体 将使用表达HPV 16和18 E6和E7基因的TA-HPV（TA-HPV）进行免疫接种。 在这项研究中使用。本研究的目的是：1）评价 对这种HPV 16/18，E6-E7-牛痘的免疫应答 重组; 2）开发毒性数据; 3）评估当地 患者免疫应答。有可活检疾病; 4）评估 HLA表型对免疫应答的影响，5） 评估环境安全状况，以及6）确定 抗肿瘤活性。重量份将接受活的重组牛痘 接种病毒-人乳头瘤病毒疫苗2.5x106PFU 每28天在上臂进行一次划痕 4. 14分。已经进入研究。12例患者可评价。 未观察到非预期不良事件。应计费用为 仅限于14例可评价患者。免疫学数据 将为今后的研究奠定基础。"

"The presumed etiologic agent in the majority of cases of cervical carcinoma is the human papilloma virus. Since this virus produces oncogenic proteins that are foreign to the host, they should be susceptible to the immune system and less likely to escape immune surveillance. HPV, types 16, 18, and 33 are associated with 75-90% of cervical cancers. E6 and E7 are the major transforming proteins and are required for the maintenance of the transformed phenotype. The transforming activity of E6 and E7 is felt to be due to their inhibitory effects on P53 and RB, respectively. Preclinical studies have shown that immunization with non- tumorigenic transfectants expressing E7 and E6 can protect mice from subsequent challenge with tumors expressing these proteins. A live recombinant vaccinia virus HPV construct (TA-HPV) expressing the HPV 16 and 18 E6 and E7 genes will be used in this study. The objectives of this study are: 1) to evaluate the immunological response to this HPV 16/18, E6-E7-vaccinia recombinant; 2) develop data on toxicity; 3) evaluate the local immunological response in pts. with biopsiable disease; 4) evaluate the effect of HLA phenotype on the immunological response, 5) evaluate the environmental safety profile, and 6) determine antitumor activity. Pts. will receive live recombinant vaccinia virus-human papilloma virus vaccine 2.5x106PFU administered percutaneously with scarification in the upper arm every 28 days x 4. 14 pts. have been entered for the study. 12 patients are evaluable. No unexpected adverse events have been seen. Accrual will be limited to a total of 14 evaluable patients. The immunological data will form the basis for future studies."