Schwarzenberger P, Harrison L, Weinacker A, Gaumer R, Theodossiou C, Summer W, Ye P, Marrogi A J, Ramesh R, Freeman S, Kolls J
Department of Medicine, LSUMC, New Orleans, USA.
J La State Med Soc. 1998 Apr;150(4):168-74.
Malignant mesothelioma (MM) is a tumor of the pleura for which there is no satisfactory treatment. It is an almost universally fatal disease, 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 MM, new modes of treatment are 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 untransduced tumor cells are killed by a so-called bystander effect. We are describing a Phase I clinical gene therapy trial for MM, which we are presently conducting at the Louisiana State University Medical Center of New Orleans. The purpose is to study the safety and to determine the maximal tolerated dose of an HSV-TK-transduced ovarian cancer cell line (PA1-STK cells) that is infused into the pleural cavities of patients. This infusion is followed by systemic administration of GCV. The hope is that administration of GCV will result in killing of both the transduced ovarian cancer cells as well as the nearby malignant cells.
恶性间皮瘤（MM）是一种胸膜肿瘤，目前尚无令人满意的治疗方法。它几乎是一种普遍致命的疾病，无论诊断时肿瘤处于何种阶段。目前的治疗方式包括手术、化疗和放疗，不过在一些研究系列中，这些方式都不比不治疗更具优势。由于MM患者预后不佳，迫切需要新的治疗模式。基因治疗是针对各种恶性肿瘤治疗的一个有前景的研究领域。最近的研究表明，将肿瘤细胞暴露于转导后表达单纯疱疹病毒胸苷激酶（HSV-TK）基因的细胞具有实用性。由于转导细胞表达HSV-TK，它们对抗病毒药物更昔洛韦（GCV）敏感。附近未转导的肿瘤细胞会因所谓的旁观者效应而被杀死。我们正在描述一项针对MM的I期临床基因治疗试验，目前正在新奥尔良的路易斯安那州立大学医学中心进行。目的是研究安全性，并确定注入患者胸腔的转导了HSV-TK的卵巢癌细胞系（PA1-STK细胞）的最大耐受剂量。在这种注入之后，进行GCV的全身给药。希望GCV的给药能导致转导的卵巢癌细胞以及附近的恶性细胞被杀死。
