INTRAVESICAL VACCINIA FOR RECURRENT BLADDER CANCER

浅表性膀胱癌患者的护理标准 是经尿道膀胱切除术还是在术后6周 膀胱内注射卡介苗这种方法不仅增加了外科手术 治愈率，但也缩短了失败复发的时间。 的 这种抗肿瘤作用的机制被广泛认为是 免疫学然而，没有证据表明肿瘤特异性 反应，因此，这是一个共识，肿瘤沉积物是 作为炎症的旁观者效应， 卡介苗膀胱炎为了启动肿瘤特异性免疫应答，我们 建议利用牛痘病毒重组体引入免疫 活性细胞因子进入肿瘤， 抗原呈递细胞和促免疫细胞因子的表达。 作为开发重组牛痘的必要步骤 膀胱癌的治疗策略，我们计划进行一项 卡介苗患者膀胱内接种牛痘病毒的I/II期研究 难治性浅表性膀胱癌，将解决四个关键 问题：i）膀胱内接种牛痘的安全性; 2） 膀胱内的suv基因功能 3）载体本身的免疫学效应; 和4）野生型诱导的抗肿瘤活性的“基线” 病毒载体这些研究将提供关键数据， 随后使用牛痘重组体。

The standard of care for patients with superficial bladder cancer is transurethral resection of the bladde or followed by six weeks of intravesical BCG. This approach not only increases the surgical cure rate but also prolongs the time to recurrence in failures. The mechanism of this anti-tumor effect is widely felt to be immunologic. However, there is no evidence for a tumor-specific response and thus it is a consensus that tumo deposits are eradicated as a bystander effect of the inflammation associated with the BCG-cystitis. To initiate a tumor-specific immune response, we propose to utilize vaccinia virus recombinants to introduce immune active cytokines into the tumor with a resultant recruitment of antigen presenting cells and expression of pro-immune cytokines. As a necessary step in the development of recombinant vaccinia strategies for the therapy of bladder cancer, we plan to conduct a Phase I/Il study of intravesical vaccinia virus in patients with BCG refractory superficial bladder cancer which will address four key issues: i) the safety of intravesical vaccinia; 2) the ability to sus vaccrnia gene fimction in the bladder over the course of therapy; 3) the immunologic effects of the vaccinia vecto itself; and 4) the "baseline" of antitumor activity induced by the wild type viral vector. These studies will provide critical data for subsequent use of vaccinia recombinants.