PHASE I/II STUDY OF VACCINIA-HPV RECOMBINANT

痘苗-HPV 重组体的 I/II 期研究

• 批准号: 2464564
• 负责人: B L GAUSE
• 金额: --
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2464564
• 关键词: cervix neoplasms; clinical research; clinical trial phase I; female; human papillomavirus; human subject; human therapy evaluation; neoplasm /cancer vaccine; oncoproteins; recombinant virus; vaccinia virus

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 2.5x10/6PFU administered percutaneously with scarification in the upper arm every 28 days x 4. 5 pts. have been entered for the study. Environmental monitoring has shown the virus to be recoverable only from the scabs and dressings in contact with the scabs. No unexpected adverse events have been seen. Initial accrual will be 14 pts. with expansion to 35 if there is evidence of clinical or immunological activity.

在大多数宫颈癌病例中， 癌是人乳头瘤病毒。 由于这种病毒产生 对于宿主来说是外来的致癌蛋白，它们应该是 易受免疫系统的影响，不太可能逃脱免疫系统 监视 HPV 16、18和33型与75-90%的 宫颈癌 E6和E7是主要的转化蛋白， 所需的转化表型的维持。 的 E6和E7的转化活性被认为是由于它们的抑制作用。 分别对P53和RB的影响。 临床前研究表明， 用表达E7和E6非致瘤性转染子免疫可 保护小鼠免受表达这些的肿瘤的后续攻击 proteins. 活重组痘苗病毒HPV构建体（TA-HPV） 表达HPV 16和18 E6和E7基因的细胞将用于本研究。 本研究的目的是：1）评价免疫学 对这种HPV 16/18，E6-E7-牛痘重组体的反应; 2）开发关于 毒性; 3）评价患者的局部免疫反应。与 可活检疾病; 4）评估HLA表型对疾病的影响 免疫反应，5）评价环境安全性，和 6)测定抗肿瘤活性。 重量份将接受活的重组 接种牛痘病毒-人乳头瘤病毒疫苗2.5x10/6PFU 每28天在上臂进行一次划痕，共4次。 5 重量份已经进入研究。 环境监测显示， 病毒只能从接触的结痂和敷料中恢复 有结痂的人 未观察到非预期不良事件。 初始 累积将为14例患者。如果有证据表明， 临床或免疫活性。