Clinical Trials in Mesothelioma

间皮瘤的临床试验

• 批准号: 7133573
• 负责人: DANIEL STERMAN
• 金额: $ 25.44万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7133573
• 关键词: birth; clinical trial phase I; clinical trials; gene therapy; genes; immune response; mesothelioma; neoplasm /cancer

The treatment of malignant mesothelioma (MPM) remains inadequate. New therapies, such as gene therapy or immuno-gene therapy, are desperately needed. This Project is based on a previous series of Phase I clinical trials using recombinant, replication-deficient adenoviral (Ad) vectors containing the Herpes Simplex Thymidine Kinase (HSVtk) gene in 34 MPM patients. Significant intratumoral HSVtk gene transfer was achieved and some radiographic and clinical responses were noted, including 2 patients who had durable complete responses in delayed fashion, highly suggestive of anti-tumor immune responses. On this basis, the focus of laboratory and clinical work was shifted to genetic immunotherapy of thoracic malignancies. Based on strong preclinical data, a new Phase I clinical trial using a single dose of intrapleural adenoviral interferon beta (Ad.lFN-beta) for patients with MPM and malignant pleural effusions (MPE) was conducted. The approach was safe and a number of immunologic responses, as well as clinical responses were observed. The goal of this Project is to continue and extend these clinical trials aimed at patients with mesothelioma. In the first aim, a Phase 1 trial will be conducted to assess the safety, toxicity profile, immune responses, and clinical effect of two intrapleural doses of Ad.lFN-beta for patients with MPE/MPM. Specific Aims 2 and 3 will consist of Phase 2 clinical trials testing approaches in patients with MPM that were developed from our preclinical studies to augment efficacy. Aim 2 will determine the efficacy and immune responses associated with the delivery of two doses of Ad.lFN-beta as neo-adjuvant therapy in combination with surgical debulking and adjuvant COX-2 inhibitors in patients with MPM. Aim 3 will determine the efficacy and immune responses associated with the delivery of two doses of Ad.lFN-beta in combination with chemotherapy and adjuvant COX-2 inhibitors in patients with MPM. In Aim 4, investigators will begin the steps needed to develop an adoptive immunotherapy trial using genetically engineering T-lymphocytes reactive against mesothelin for patients with mesothelioma and other tumors expressing this tumor antigen after preclinical optimization.

恶性间皮瘤（MPM）的治疗仍然不足。新疗法，如基因疗法 或者免疫基因疗法，是迫切需要的。该项目是基于前一系列的第一阶段 使用含有单纯疱疹病毒的重组复制缺陷型腺病毒（Ad）载体的临床试验 34例MPM患者胸苷激酶（HSVtk）基因检测结果。显著的瘤内HSVtk基因转移是 达到，并注意到一些放射学和临床反应，包括2名患者， 以延迟的方式完全应答，高度提示抗肿瘤免疫应答。在此基础上， 实验室和临床工作的重点转移到胸部恶性肿瘤的遗传免疫治疗。 基于强大的临床前数据，一项新的I期临床试验使用单剂量胸膜内腺病毒 干扰素β（Ad. IFN-β）治疗MPM和恶性胸腔积液（MPE）患者。 该方法是安全的，许多免疫反应，以及临床反应， 观察该项目的目标是继续和扩展这些针对以下患者的临床试验： 间皮瘤在第一个目标中，将进行1期试验以评估安全性、毒性特征、免疫原性和耐受性。 结果显示，两种胸膜内剂量的Ad. IFN-beta对MPE/MPM患者的治疗反应和临床效果。具体 目标2和3将包括在MPM患者中测试方法的2期临床试验， 从我们的临床前研究中开发出来以增强疗效。目的2将确定疗效和免疫 与递送两个剂量的Ad. IFN-β作为新辅助疗法组合 与手术减积和辅助考克斯-2抑制剂的MPM患者。目标3将决定 与递送两个剂量的Ad. IFN-β联合 化疗和辅助考克斯-2抑制剂治疗MPM患者。在目标4中，研究人员将开始 开发使用基因工程T淋巴细胞的过继免疫治疗试验所需的步骤 对于间皮瘤和表达该肿瘤抗原的其他肿瘤患者， 临床前优化后。