Treatment of relapsed malignant glioma with an adenoviral vector containing the herpes simplex thymidine kinase gene followed by ganciclovir
Treatment of relapsed malignant glioma with an adenoviral vector containing the herpes simplex thymidine kinase gene followed by ganciclovir
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DOI：
10.1016/s1525-0016(03)00100-x
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发表时间：
2003-06-01
影响因子：
12.4
通讯作者：
Avezaat, C
中科院分区：
文献类型：
--
作者：
Smitt, PS;Driesse, M;Avezaat, C
在1998年11月至2001年12月期间，我们治疗了14例晚期复发的高级别胶质瘤患者，总剂量为4.6×10(8)、4.6×10(9)、4.6×10(10)或4.6×10(11)病毒颗粒(VP)，该载体携带由腺病毒主要晚期启动子(IG.Ad.MLPI.TK)驱动的单纯疱疹病毒胸苷激酶基因，随后接受更昔洛韦(GCV)治疗。VP与感染单位之比为40。该载体在术中伤口床上注射50次，每次0.2毫升(总容量10毫升)。这项研究的主要目标是确定这种治疗的安全性，并确定最大耐受剂量(MTD)。注射所有剂量的IG.Ad.MLPI.TK后再注射GCV是安全的，未达到MTD。所有患者在基因治疗后1~24个月(中位数3.5个月)肿瘤复发或进展。中位生存期为4个月。4例患者在基因治疗后存活超过1年。一名患者在治疗29个月后仍活着，组织学证实肿瘤进展。10名患者在治疗后8个月内死亡，全部死于肿瘤的进展。5例患者直视下可见可测量的残留肿瘤(
Between November 1998 and December 2001, we treated 14 patients with advanced recurrent high-grade gliomas with a total dose of 4.6 x 10(8), 4.6 x 10(9), 4.6 x 10(10), or 4.6 x 10(11) viral particles (VP) of a replication-incompetent adenoviral vector harboring the herpes simplex virus thymidine kinase gene driven by the adenoviral major late promoter (IG.Ad.MLPI.TK), followed by ganciclovir (GCV) treatment. The VP-to-infectious-unit ratio was 40. The vector was administered by 50 intraoperative wound-bed injections of 0.2 ml each (total volume 10 ml). The study's primary objective was to determine the safety of this treatment and establish the maximum tolerated dose (MTD). Injection of all doses of IG.Ad.MLPI.TK followed by GCV was safely tolerated and MTD was not reached. All patients had recurrence or progression of the tumor 1-24 months (median 3.5 months) after gene therapy. The overall median survival was 4 months. Four patients survived longer than 1 year following gene therapy. One patient is still alive, with histologically confirmed progression of the tumor, 29 months after treatment. Ten patients died within 8 months of treatment, all from progression of the tumor. In 5 patients residual and measurable tumor was visible on the direct (