TREATMENT PROTOCOL FOR ALLOVECTIN-7 IN METASTATIC CANCER BY DIRECT GENE TRANSFER

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一项扩展方案，允许参加Vical 301研究并有肿瘤反应的受试者继续接受治疗。本研究还将允许仅在301年参与DTIC组的受试者能够获得基因治疗产品Allovectin-7。同种异体素-7是一种含有HLA-B7蛋白基因的基因治疗产品。HLA-B7蛋白导致含有它的细胞被免疫系统识别为外来入侵者。HLA-B7基因包含在质粒内。这些质粒将与脂质混合，并通过针注射插入肿瘤。一旦引入肿瘤，含有质粒DNA的细胞就会产生蛋白质，根据动物研究，这些蛋白质被认为会刺激肿瘤组织的反射。这项研究将在全国多个地点进行，将招募大约12名受试者。这种治疗需要将基因物质直接注射到受试者的肿瘤中。这些基因注射被认为能诱发对癌症的免疫反应。使用基因疗法，免疫疗法Allovectin-7，可能提供一种毒性较小，但可能同样有效的替代rif和rIL-2在化疗-生物联合治疗中的使用。即使使用Allovectin-7不能提高应答率，但这种免疫疗法与DTIC联合使用可能会延长疾病进展的时间，或产生更持久的应答，从而为患者带来切实的临床益处。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is an extended protocol to allow subjects who have participated in the Vical 301 study and have had a tumor response to continue on treatment. This study will also allow subjects who have participated on the DTIC arm only in 301 to be able to get the gene therapy product Allovectin-7. Allovectin-7 is a gene therapy product containing the gene for the HLA-B7 protein. The HLA-B7 protein causes the cells which contain it to be recognized as a foreign invader by the immune system. The HLA-B7 gene is contained within the plasmid. These plasmids will be mixed with lipids and inserted into the tumor by needle injection. Once introduced into the tumor, the cells containing the plasmid DNA produce proteins which, based on animal studies, are thought to stimulate tumor tissue refection. This research study will be conducted at multiple sites across the country and will enroll approximately 12 subjects. This treatment requires injection of the gene substance directly into the subject's tumor(s). These gene injections are thought to induce an immune response to the cancer. The use of gene therapy immunotherapeutic, Allovectin-7, may provide a less toxic, but potentially equally effective alternative to the use of rINF and rIL-2 in a chemo-biotherapy combination therapy. Even if the rate of response were not to improve using Allovectin-7, the use of this immunotherapeutic in combination with DTIC may however, either extend the time to disease progression, or produce more durable responses resulting in tangible clinical benefit to patients.