Clinical Trials in Mesothelioma

该项目的总体假设是，免疫基因治疗可以成功地用于恶性胸膜间皮瘤(MPM)的治疗。该项目将继续将项目2和项目3的临床前研究结果转移到尖端临床试验(床边到床边)；并将临床数据和样本返回项目2和3，以便在下一轮临床试验(床边到床边)中有所改进。 该项目的第一个重点是继续和扩大成功的试验，使用胸膜腔内注射表达1型干扰素的腺病毒(Ad.1FN)。基于项目2的临床前数据，启动了一项1/2期试验，将两剂Ad.干扰素-α(间隔3天)与同时给予塞来昔布相结合，两周后进行4-6个一线(培美曲塞/顺铂/)或二线(吉西他滨/卡铂)化疗。这项建议的目标1是完成2期试验，以确定应答率是否保证将该疗法转移到由行业或合作团体进行的更大规模的随机2期或3期试验。该项目的第二个重点是使用带有嵌合抗原受体(CARS)的T细胞进行过继T细胞治疗，该T细胞最初针对间皮瘤肿瘤表面抗原--间皮蛋白。考虑到其他一些汽车的潜在安全问题，将进行一项试验，使用转导GMP级mRNA的T细胞(目标2A)。由于汽车表达时间有限，如果有的话

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