临床试验表明，对恶性脑瘤开发出的基因疗法具有安全性，辅助的放射疗法也不影响基因疗法的安全性。
神经胶质瘤
新的疗法使用AdV-tk腺病毒载体，这一载体运输到癌细胞后，激活能杀死细胞的药物。同时这一疗法可激活对肿瘤的免疫应答。相关的研究发表在Clinical Oncology期刊网络版上。
研究人员称，这是首次对神经胶质瘤患者采用基因疗法和放射疗法。很多人关注这2种疗法对病人的毒理作用，然而事实上不存在这一情况。我们还不知道新疗法是否能提高病人的存活时间，但这一发现足够令人鼓舞了。
每年，美国新出现大约18500 位神经胶质瘤患者，以及近13000位患者死于这种恶性肿瘤。神经胶质瘤是一种最常见、最致命的肿瘤，一旦被诊断，病人的存活时间大概是15个月。
10位神经胶质瘤患者和2位星形细胞瘤患者参与临床试验，治疗流程如下：
取出肿瘤后，神经外科医生在肿瘤中注射含有疱疹病毒胸苷激酶（AdV-tk）重组载体的试剂液，载体携带胸苷激酶的编码基因，感染的癌细胞表达这一蛋白酶；
患者再服用抗疱疹病毒药物valacyclovir 2个星期；
在癌细胞中，AdV-tk 激酶能够把 valacyclovir 催化成DNA构件分子，然而快速生长的癌细胞不能利用它合成DNA，最终因DNA合成受阻而死亡；
放射治疗在基因疗程进行一半时采用。物理疗法能够损害癌细胞正在修复的DNA结构。
除了整体存活时间提高外，T淋巴细胞的数量在肿瘤细胞中明显地上升。这表明基因疗法能够刺激对肿瘤的免疫应答，因而产生免疫治疗的副作用。（生物探索译 Pobee）
生物探索推荐英文摘要
Phase IB Study of Gene-Mediated Cytotoxic Immunotherapy Adjuvant to Up-Front Surgery
and Intensive Timing Radiation for Malignant Glioma
Abstract
Purpose Despite aggressive therapies, median survival for malignant gliomas is less than 15 months. Patients with unmethylated O6-methylguanine–DNA methyltransferase (MGMT) fare worse, presumably because of temozolomide resistance. AdV-tk, an adenoviral vector containing the herpes simplex virus thymidine kinase gene, plus prodrug synergizes with surgery and chemoradiotherapy, kills tumor cells, has not shown MGMT dependency, and elicits an antitumor vaccine effect.
Patients and Methods Patients with newly diagnosed malignant glioma received AdV-tk at 3 × 1010, 1 × 1011, or 3 × 1011 vector particles (vp) via tumor bed injection at time of surgery followed by 14 days of valacyclovir. Radiation was initiated within 9 days after AdV-tk injection to overlap with AdV-tk activity. Temozolomide was administered after completing valacyclovir treatment.
Results Accrual began December 2005 and was completed in 13 months. Thirteen patients were enrolled and 12 completed therapy, three at dose levels 1 and 2 and six at dose level 3. There were no dose-limiting or significant added toxicities. One patient withdrew before completing prodrug because of an unrelated surgical complication. Survival at 2 years was 33% and at 3 years was 25%. Patient-reported quality of life assessed with the Functional Assessment of Cancer Therapy-Brain (FACT-Br) was stable or improved after treatment. A significant CD3+ T-cell infiltrate was found in four of four tumors analyzed after treatment. Three patients with MGMT unmethylated glioblastoma multiforme survived 6.5, 8.7, and 46.4 months.
Conclusion AdV-tk plus valacyclovir can be safely delivered with surgery and accelerated radiation in newly diagnosed malignant gliomas. Temozolomide did not prevent immune responses. Although not powered for efficacy, the survival and MGMT independence trends are encouraging. A phase II trial is ongoing.
