PHASE I/II STUDY OF VACCINIA-HPV RECOMBINANT

痘苗-HPV 重组体的 I/II 期研究

• 批准号: 6123747
• 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/6123747
• 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 2.5x106PFU 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."

“大多数疾病的推定病原体 宫颈癌病例是人乳头瘤病毒。既然是这样 病毒产生与宿主无关的致癌蛋白，它们 应该容易受到免疫系统的影响，而且不太可能 逃脱免疫监视。HPV，类型16、18和33是 与75%-90%的宫颈癌有关。E6和E7是 主要的转化蛋白，是维持 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， 分别进行了分析。临床前研究表明，使用 表达E7和E6的非致瘤转基因细胞可保护 小鼠在随后的肿瘤攻击中表达这些 蛋白质。重组痘苗病毒HPV活载体的构建 (Ta-HPV)表达HPV16和18E6和E7基因将是 在这项研究中使用。本研究的目的是：1)评估 HPV16/18、E6-E7疫苗的免疫学应答 重组；2)开发毒性数据；3)评估局部 PTS的免疫学反应。有可活组织的疾病；4)评估 人类白细胞抗原表型对免疫应答的影响 评估环境安全概况，并6)确定 抗肿瘤活性。PTS。将接种活的重组牛痘 病毒-人乳头瘤病毒疫苗2.5x106PFU接种 上臂每隔28天出现一次皮肤划痕 4.14分。已经报名参加了这项研究。12例患者可评价。 没有看到任何意想不到的不利事件。应计项目将为 限制为总共14名可评估的患者。免疫学数据 将构成未来研究的基础。