Recombinant adenoviral vectors have adjuvant activity and stimulate T cell responses against tumor cells
Recombinant adenoviral vectors have adjuvant activity and stimulate T cell responses against tumor cells
复制标题
DOI：
10.1038/sj.gt.3301251
复制
发表时间：
2000-08-01
期刊：
影响因子：
5.1
通讯作者：
Hoeben, RC
中科院分区：
文献类型：
--
作者：
Geutskens, SB;van der Eb, MM;Hoeben, RC
针对腺病毒的宿主免疫应答形成了它们用作基因治疗载体以治疗遗传缺陷的主要障碍。尽管如此，它们仍是癌症实验基因治疗方案中体内基因转移的优选载体。在这篇文章中，我们证明了腺病毒介导的转移人白细胞介素-2 cDNA在大鼠结肠直肠癌肝转移的CC 531模型中的抗肿瘤功效。瘤内给予10（8）空斑形成单位的表达hIL-2的腺病毒载体AdCAIL-2，导致80%的注射肿瘤停止生长。在接受AdCnull（一种具有相同病毒骨架但缺乏转基因表达的载体）的对照组中，没有一个肿瘤有反应。然而，用该载体进行肿瘤内治疗显著增强了由全身性IL-2蛋白治疗诱导的肿瘤消退，其用作阳性对照。此外，我们表明，通过进行迟发型超敏反应试验，AdCnull瘤内注射时，增强识别肿瘤抗原的T淋巴细胞与IL-2表达载体瘤内治疗相同的程度。复制缺陷型腺病毒似乎在腺嘌呤介导的免疫治疗中具有治疗优势：即使不表达转基因的腺病毒载体也显示出佐剂活性并刺激抗肿瘤免疫应答。
The host-immune response against adenoviruses forms a major obstacle for their use as gene therapy vectors for treatment of genetic defects. None the less, they are the preferred vectors for in vivo gene transfer in experimental gene therapy protocols for cancer. In this article we demonstrate the antitumor efficacy of adenovirus-mediated transfer of human interleukin-2 cDNA in the rat-CC531 model for hepatic metastases of colorectal cancer intratumoral administration of 10(8) plaque-forming units of the hIL-2-expressing adenoviral vector, AdCAIL-2, resulted in a cessation of tumor growth in 80% of the injected tumors. In control groups receiving AdCnull, a vector with the same viral backbone, but lacking transgene expression, none of the tumors responded. However, intratumoral treatment with this vector significantly enhanced tumor regression induced by systemic IL-2 protein treatment, which was used as a positive control. In addition we show, by performing delayed-type of hypersensitivity assays, that AdCnull when injected intratumorally enhances recognition of tumor antigens by T lymphocytes to the same extent as intratumoral treatment with the IL-2-expressing vector. The replication-deficient adenoviruses appear to have a therapeutic advantage in cytokine-mediated immunotherapy: even adenovirus vectors that do not express a transgene, show adjuvant activity and stimulate an antitumor immune response.