Sandmair A M, Loimas S, Puranen P, Immonen A, Kossila M, Puranen M, Hurskainen H, Tyynelä K, Turunen M, Vanninen R, Lehtolainen P, Paljärvi L, Johansson R, Vapalahti M, Ylä-Herttuala S
A.I. Virtanen Institute, University of Kuopio, FIN-70211 Kuopio, Finland.
Hum Gene Ther. 2000 Nov 1;11(16):2197-205. doi: 10.1089/104303400750035726.
Herpes simplex virus thymidine kinase (HSV tk) gene therapy combined with ganciclovir (GCV) medication is a potential new method for the treatment of malignant glioma. We have used both retrovirus-packaging cells (PA317/tk) and adenoviruses (Adv/tk) for gene therapy for malignant glioma. Retrovirus-packaging cells were used for eight tumors in seven patients and adenoviruses were used for seven tumors in seven patients. As a control group, seven tumors in seven patients were transduced with lacZ marker gene 4-5 days before tumor resection. Safety and efficacy of the gene therapy were studied with clinical evaluation, blood and urine samples, MRI follow-up, and survival of the patients. Four patients with adenovirus injections had a significant increase in anti-adenovirus antibodies and two of them had a short-term fever reaction. Frequency of epileptic seizures increased in two patients. No other adverse events possibly related to gene therapy were detected. In the retrovirus group, all treated gliomas showed progression by MRI at the 3-month time point, whereas three of the seven patients treated with Adv/tk remained stable (p < 0.05). Mean survival times for retrovirus, adenovirus, and control groups were 7.4, 15.0, and 8. 3 months, respectively. The difference in the survival times between the adenovirus and retrovirus groups was significant (p < 0.012). It is concluded that HSV tk gene therapy is safe and well tolerated. On the basis of these results further trials are justified, especially with adenovirus vectors.
单纯疱疹病毒胸苷激酶（HSV tk）基因疗法联合更昔洛韦（GCV）药物治疗是一种治疗恶性胶质瘤的潜在新方法。我们已使用逆转录病毒包装细胞（PA317/tk）和腺病毒（Adv/tk）进行恶性胶质瘤的基因治疗。逆转录病毒包装细胞用于7例患者的8个肿瘤，腺病毒用于7例患者的7个肿瘤。作为对照组，7例患者的7个肿瘤在肿瘤切除前4 - 5天用lacZ标记基因进行转导。通过临床评估、血液和尿液样本、MRI随访以及患者生存情况研究了基因治疗的安全性和有效性。4例接受腺病毒注射的患者抗腺病毒抗体显著增加，其中2例有短期发热反应。2例患者癫痫发作频率增加。未检测到其他可能与基因治疗相关的不良事件。在逆转录病毒组中，所有接受治疗的胶质瘤在3个月时间点通过MRI显示进展，而7例接受Adv/tk治疗的患者中有3例保持稳定（p < 0.05）。逆转录病毒组、腺病毒组和对照组的平均生存时间分别为7.4个月、15.0个月和8.3个月。腺病毒组和逆转录病毒组生存时间的差异具有显著性（p < 0.012）。结论是HSV tk基因治疗安全且耐受性良好。基于这些结果，进一步试验是合理的，特别是使用腺病毒载体的试验。
