Clinical Trials in Mesothelioma

间皮瘤的临床试验

基本信息

批准号：
8291479
负责人：
DANIEL STERMAN
金额：
$ 30.28万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-03-01 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8291479
关键词：
Adenovirus Vector Adenoviruses Adjuvant Adoptive Immunotherapy Adverse effects Antigen Receptors Back Blood Carboplatin Catchment Area Cells Chest Cisplatin Clinical Clinical Data Clinical Research Clinical Trials Data Delaware Development Diagnosis Dose Engineering Funding Goals Human Immune response Immunologics Immunotherapy In Situ Individual Industry Inflammatory Injection of therapeutic agent Institutional Review Boards Instruction Interferon Alfa-2b Interferon-alpha Interferons Intravesical Instillation Knowledge Life Lymphocyte Malignant Neoplasms Malignant Pleural Mesothelioma Malignant mesothelioma Malignant neoplasm of urinary bladder Mesothelioma Messenger RNA Normal tissue morphology PTGS2 gene Patients Pemetrexed Phase Phase II Clinical Trials Phase III Clinical Trials Play Pleural Pleural Diseases Production Randomized Research Personnel Role Safety Series Specimen Staging Subfamily lentivirinae Surface Antigens T cell therapy T-Cell Receptor T-Lymphocyte TGFB1 gene Time Travel Viral Vector Work base bench to bedside celecoxib chemotherapy cytokine gemcitabine gene therapy immuno-gene therapy inhibitor/antagonist intravenous administration killings mesothelin neoplastic cell new technology novel novel strategies pre-clinical pre-clinical research programs receptor expression response tumor tumor immunology vector

项目摘要

The overall hypothesis of this project is that immuno-gene therapy can be used successfully to treat malignant pleural mesothelioma (MPM). The Project will continue to move the preclinical findings from Projects 2 and 3 into cutting-edge clinical trials (bench-to-bedside); and to provide clinical data and specimens back to Projects 2 and 3 to inform improvements in the next iteration of clinical trials (bedside-to bench). The first focus of this project is to continue and extend successful trials using intrapleural injections of an adenovirus (Ad) expressing type 1 interferon (Ad.lFN). Based on preclinical data from Project 2, a Phase 1/2 trial was initiated combining two Ad.IFN-alpha doses (given 3 days apart) with concomitant Celecoxib administration, followed two weeks later by 4-6 cycles of either front-line (pemetrexed/cisplatin/) or second-line (gemcitabine/carboplatin) chemotherapy. Aim 1 of this proposal is to complete the Phase 2 trial to determine if the response rate warrants moving this therapy to a larger randomized Phase 2 or 3 trial by either industry or cooperative groups. The second focus of the Project is adoptive T cell therapy using T cells with chimeric antigen receptors (CARs) initially targeted to the mesothelioma tumor surface antigen, mesothelin. Given potential safety concerns with some other CARs, a trial using T-cells transduced with GMP grade mRNA will be conducted (Aim 2A). Since CAR expression time is limited, if any

该项目的总体假设是免疫基因疗法可以成功用于治疗恶性胸膜间皮瘤（MPM）。该项目将继续将项目 2 和 3 的临床前研究结果转化为尖端临床试验（从实验室到临床）；并向项目 2 和 3 提供临床数据和样本，以便为下一次临床试验（从床边到工作台）的改进提供信息。该项目的首要重点是继续并扩展使用表达 1 型干扰素 (Ad.lFN) 的腺病毒 (Ad) 胸膜内注射的成功试验。根据项目 2 的临床前数据，启动了一项 1/2 期试验，将两剂 Ad.IFN-α 剂量（间隔 3 天给药）与塞来考昔联合给药，两周后进行 4-6 个周期的任一一线治疗（培美曲塞/顺铂/）或二线（吉西他滨/卡铂）化疗。该提案的目标 1 是完成 2 期试验，以确定缓解率是否值得由行业或合作团体将该疗法转移到更大规模的随机 2 期或 3 期试验。该项目的第二个重点是过继性 T 细胞疗法，使用带有嵌合抗原受体 (CAR) 的 T 细胞，最初靶向间皮瘤肿瘤表面抗原间皮素。考虑到其他一些 CAR 的潜在安全性问题，将进行一项使用 GMP 级 mRNA 转导的 T 细胞的试验（目标 2A）。由于CAR表达时间有限，如果有的话