Increased injection number enhances adenoviral genetic radiotherapy.

H J Mauceri, L P Seung, W L Grdina, K A Swedberg, R R Weichselbaum
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引用次数: 13

Abstract

Intratumoral injection of an adenoviral vector containing radiation-inducible DNA sequences of the early growth response gene (Egr-1) promoter ligated to a cDNA encoding tumor necrosis factor-alpha (TNF-alpha; Ad.Egr-TNF) increases the radiation killing of a human radioresistant xenograft (SQ-20B). Viral dose-escalation experiments demonstrated that SQ-20B growth inhibition correlated with viral titer. Injection of 5 x 10(8) PFU Ad.Egr-TNF produced regression to a mean volume of 22 +/- 13% of the original tumor volume, 1 x 10(8) PFU to a mean of 62 +/- 24%, and 5 x 10(7) PFU to a mean of 67 +/- 27%. No regression was observed when tumors were injected with 1 x 10(7) PFU Ad.Egr-TNF or with the null viral vector (Ad.null). When two injections of vector (2 x 10(8) PFU Ad.Egr-TNF) were combined with 50 Gy, a significant increase in tumor regression was observed compared with injection of buffer, Ad.Egr-TNF, or 50 Gy. The interactive killing between TNF and radiation was enhanced significantly (P = 0.05) when the number of injections was increased from two to five while maintaining a constant viral titer (2 x 10(8) PFU Ad.Egr-TNF) and a constant radiation dose (50 Gy). Significant TNF-alpha levels were present in irradiated vs. unirradiated tumors following injection with Ad.Egr-TNF. Taken together, these data suggest that the volumetric reduction produced by the combined effects of Ad.Egr-TNF and radiation is enhanced with increasing vector concentration and the number of vector injections.

注射次数增加可增强腺病毒基因放疗效果。
肿瘤内注射含有早期生长反应基因(Egr-1)启动子连接到编码肿瘤坏死因子- α (tnf - α)的cDNA的辐射诱导DNA序列的腺病毒载体;Ad.Egr-TNF)增加了人类抗辐射异种移植物(SQ-20B)的辐射杀伤。病毒剂量递增实验表明,SQ-20B的生长抑制作用与病毒滴度相关。注射5 × 10(8) PFU Ad。Egr-TNF使平均肿瘤体积回归到原始肿瘤体积的22 +/- 13%,1 × 10(8) PFU回归到平均62 +/- 24%,5 × 10(7) PFU回归到平均67 +/- 27%。当肿瘤注射1 × 10(7) PFU Ad时,未观察到肿瘤消退。Egr-TNF或与空病毒载体(Ad.null)。当两次注射载体(2 × 10(8) PFU Ad. egr - tnf)联合50 Gy时,与注射缓冲液Ad相比,肿瘤消退明显增加。Egr-TNF,或50 Gy。当注射次数从2次增加到5次,同时保持恒定的病毒滴度(2 × 10(8) PFU Ad.Egr-TNF)和恒定的辐射剂量(50 Gy)时,TNF与辐射的相互作用杀伤显著增强(P = 0.05)。注射Ad.Egr-TNF后,辐照肿瘤与未辐照肿瘤的tnf - α水平显著升高。综上所述,这些数据表明,由Ad的综合作用产生的体积减少。Egr-TNF和辐射随载体浓度和载体注射次数的增加而增强。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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