PHASE I/II STUDY OF VACCINIA-HPV RECOMBINANT

大多数宫颈病变的推定病因 癌症是人类乳头状瘤病毒。因为这种病毒会产生 与宿主无关的致癌蛋白，它们应该是 易受免疫系统影响，不太可能逃脱免疫 监视系统。HPV 16、18和33型与75%-90%的 宫颈癌。E6和E7是主要的转化蛋白， 保持转化的表型所必需的。这个 E6和E7的转化活性被认为是由于它们的抑制作用 对P53和Rb的影响。临床前研究表明， 表达E7和E6的非致瘤转染体免疫可 保护小鼠免受随后表达这些基因的肿瘤的攻击 蛋白质。重组痘苗病毒活载体(TA-HPV) 表达HPV16和18E6和E7基因将在本研究中使用。 这项研究的目的是：1)评估免疫学 对这种HPV16/18、E6-E7-牛痘重组疫苗的反应；2)开发关于 毒性；3)评价PTS患者的局部免疫反应。使用 4)评价人类白细胞抗原表型对患者预后的影响。 免疫反应，5)评估环境安全概况，以及 6)抗肿瘤活性测定。PTS。将收到活的重组人 痘苗病毒-人乳头瘤病毒疫苗2.5×10/6PFU接种 上臂每隔28天x 4.5次出现一次皮肤划痕 PTS。已经报名参加了这项研究。环境监测显示 病毒只能从接触过的结痂和敷料中恢复 满身的伤疤。没有看到任何意想不到的不利事件。首字母 应计分为14分。扩展到35，如果有证据表明 临床或免疫学活动。

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.