TREATMENT OF MALIGNANT PLEURAL MESOTHELIOMA W/ GENE MODIFIED CANCER CELL LINES

恶性间皮瘤是一种起源于胸膜的肺癌，由职业暴露于石棉引起。间皮瘤在路易斯安那州东南部，特别是新奥尔良地区，发病率过高。该市拥有大型造船工业和全国最大的石棉制造厂之一；该市这种疾病的发病率高得不成比例。这种癌症没有令人满意的治疗方法，而且无论诊断时肿瘤处于哪个阶段，它几乎都是致命的。目前的治疗方式包括手术、化疗和放射治疗，尽管在一些系列中，这些方式都不优于根本不治疗。由于恶性间皮瘤患者预后不佳，迫切需要一种新的治疗模式。基因疗法是治疗各种恶性肿瘤的一个很有前途的研究领域。最近的研究表明，将肿瘤细胞暴露于转导表达胸苷激酶单纯疱疹病毒基因(HSV-TK)的细胞中是有用的。由于表达HSV-TK，转导的细胞对抗病毒药物更昔洛韦(GCV)敏感。附近的肿瘤细胞被所谓的旁观者效应杀死。在这个方案中，我们提出了一项I期试验，将HSV-TK转导的卵巢癌细胞引入恶性胸膜间皮瘤患者的胸腔，然后全身应用更昔洛韦。希望更昔洛韦能杀死转导的卵巢癌细胞以及附近的恶性间皮瘤细胞。

Malignant mesothelioma is a lung cancer originating from the pleura and is caused by occupational exposure to asbestos. Mesothelioma is highly overrepresented in South East Louisiana, specifically the New Orleans area. The city had a large shipyard industry and one of the largest asbestos manufacturing plants in the country; it has a disproportionately large incidence of this disease. There is no satisfactory treatment for this cancer and it is almost universally fatal, regardless of the stage of the tumor at the time of diagnosis. Current treatment modalities include surgery, chemotherapy, and radiation therapy, although in some series none of these modalities is superior to no treatment at all. Because of the dismal prognosis for patients with malignant mesothelioma, a new mode of treatment is desperately needed. A promising area of research into the treatment of various malignancies is gene therapy. Recent studies have demonstrated the utility of exposing tumor cells to cells transduced to express the Herpes simplex virus gene for thymidine kinase (HSV-TK). By virtue of their expression of HSV-TK, the transduced cells are rendered susceptible to the antiviral drug, ganciclovir (GCV). Nearby tumor cells are killed by a so-called bystander effect. In this protocol, we propose a Phase I trial to introduce HSV-TK transduced ovarian cancer cells into the pleural cavities of patients with malignant pleural mesothelioma, followed by systemic administration of ganciclovir. The hope is that administration of ganciclovir will result in killing of the transduced ovarian cancer cells as well as the nearby malignant mesothelioma cells.