RADIATION AND IL3 GENE THERAPY OF PROSTATE CANCER

该计划的总体目标是开发一种新的治疗方法 对于前列腺癌来说，它利用了辐射之间的协同效应 IL-3基因治疗。我们在之前的研究中已经表明，IL-3 使肿瘤对辐射效应敏感，同时诱导 能够消除远处转移的系统抗肿瘤免疫。 拟议的临床前小鼠前列腺癌模型研究已经 旨在确定这些局部和全身抗肿瘤药物 在肿瘤发生前、期间或之后暴露IL-3可使效果最佳 放射治疗。我们选择了转基因的同种异体 成纤维细胞将IL-3运送到肿瘤部位。在我们之前的研究中， 转导细胞因子可获得相同的抗肿瘤效果 肿瘤细胞、同基因成纤维细胞和同种异体成纤维细胞。为 从实际考虑，我们将产生一个人类的主细胞库 转IL-3基因的同种异体成纤维细胞系 用于后续临床试验的载体。成功开发 联合放射治疗和IL-3基因治疗以增强局部辐射 治疗和提供有效的系统治疗将会有很大的帮助 对前列腺癌的治疗有重要意义。 建议的商业应用 大约50%的前列腺癌患者被认为患有 治愈的局部疾病会复发，局部或转移 肿瘤。这项计划中将要开发的治疗方法旨在 提高局部放疗疗效，激发抗肿瘤作用 免疫治疗转移性疾病。这项技术的成功开发 治疗将在未来产生重大的临床应用。

The overall objective of this program is to develop a novel treatment for prostate cancer which exploits synergistic effects between radiation and IL-3 gene therapy. We have shown in previous studies that IL-3 sensitizes tumors to the effects of radiation and simultaneously induces systemic anti-tumor immunity capable of eliminating distant metastases. The proposed pre-clinical murine prostate tumor model studies have been designed to determine whether these local and systemic anti-tumor effects may be optimized by IL-3 tumor exposure before, during or after radiotherapy. We have chosen genetically modified allogeneic fibroblasts to deliver IL-3 to the tumor site. In our previous studies, equivalent anti-tumor effects were obtained with cytokine transduced tumor cells, syngeneic fibroblasts and allogeneic fibroblasts. For practical considerations, we will generate a master cell bank of a human allogeneic fibroblast cell line transfected with an IL-3 expression vector for subsequent use in clinical trials. Successful development of combined radiation and IL-3 gene therapy to enhance local radiation treatment and provide effective systemic therapy will have very significant implications for the treatment of prostate cancer. PROPOSED COMMERCIAL APPLICATION Approximately 50 percent of prostate cancer patients presumed to have curative localized disease will relapse with either local or metastatic tumors. The therapy to be developed in this program is designed to improve the efficacy of local radiotherapy and to stimulate anti-tumor immunity to treat metastatic disease. Successful development of this treatment will result in significant future clinical applications.