Immune Response to Viral Vectors
Immune Response to Viral Vectors
复制标题
对病毒载体的免疫反应
DOI：
10.1007/978-1-59259-478-8_9
复制
发表时间：
1998
期刊：
影响因子：
15.1
通讯作者：
S. Eck
中科院分区：
文献类型：
--
作者：
Jason G. Smith;S. Eck
重组病毒载体是一类重要的治疗基因递送载体。然而，由于它们使受体暴露于外来蛋白质，因此宿主免疫反应是它们用于治疗人类疾病时的一个重要考虑因素。特别是，治疗上有用的病毒载体的毒性可能会限制可施用的剂量、转基因表达的持续时间以及重新施用载体的能力，所有这些都可能对治疗功效产生显着影响。腺病毒、逆转录病毒、腺相关病毒（AAV）和单纯疱疹病毒（HSV）载体受到了最多的关注，许多临床试验正在进行中，以测试它们在治疗各种遗传性和获得性疾病中的效用。特别是，正在研究腺病毒载体用于治疗多种中枢神经系统 (CNS) 和非 CNS 疾病 (1)，目前正在进行两项使用腺病毒载体治疗神经胶质瘤的临床试验 (2)。载体应用可以根据转基因表达所需的持续时间和免疫反应对靶细胞的影响进行分类。例如，纠正帕金森病 (PD) 等疾病可能需要长期的基因表达，并且对转导的细胞没有免疫反应。相比之下，基于病毒的疫苗和涉及脑肿瘤细胞免疫调节的抗癌策略可能会有效地受益于对转导细胞产生显着免疫反应的短期基因表达。在涉及基因递送酶前药疗法 (GDEPT) (3,4) 的其他临床应用中，尚不清楚对载体的免疫反应将如何影响整体疗法。在我们的研究中，我们发现连续两次注射表达HSV胸苷激酶（HSVTK）基因的腺病毒与全身更昔洛韦（GCV）相结合具有良好的耐受性。患者接受了高达 109 pfu 的病毒，同时服用大剂量的糖皮质激素，迄今为止没有明显的毒性（5；J. Alavi、K. Judy 和 S. Eck，宾夕法尼亚大学，未发表的观察结果）。
Recombinant viral vectors are an important class of therapeutic gene delivery vehicles. However, because they expose the recipient to foreign proteins, the host immune response is an important consideration in their use in the treatment of human disease. In particular, the toxicity of therapeutically useful viral vectors may limit the dose that can be administered, the duration of transgene expression, and the ability to readminister the vector, all of which may have a significant impact on therapeutic efficacy. Adenovirus, retrovirus, adeno-associated virus (AAV), and herpes simplex virus (HSV) vectors have received the most attention and many clinical trials are under way to test their utility in treating a variety of genetic and acquired disorders. Adenoviral vectors, in particular, are being studied for the treatment of several central nervous system (CNS) and non-CNS diseases (1), and two clinical trials are currently underway using adenovirus vectors to treat gliomas (2). Vector applications can be categorized on the basis of the desired duration of transgene expression and the effect of the immune response on the target cell. For example, correction of such disorders as Parkinson’ s disease (PD) will likely require long-term gene expression and no immune response to the transduced cell. In contrast, viral-based vaccines and anticancer strategies involving immune modulation of brain tumor cells may effectively benefit from short-term gene expression in the context of a significant immune response to the transduced cells. In other clinical applications involving the gene delivered enzyme-prodrug therapies (GDEPT) (3,4) it is not clear how the immune response to the vector will impact on the overall therapy. In our studies, we have found that two successive injections of adenovirus expressing the HSV thymidine kinase (HSVTK) gene in conjunction with systemic ganciclovir (GCV) has been well tolerated. Patients have received up to 109 pfu of virus with concomitant administration of large doses of glucocorticoids with no apparent toxicity to date (5; J. Alavi, K. Judy, and S. Eck, University of Pennsylvania, unpublished observations).
登录
查看更多内容
影响因子：
11.2
作者：
L. Chen;D. Waxman
通讯作者：
L. Chen;D. Waxman
影响因子：
56.9
作者：
Fearon, DT;Locksley, RM
通讯作者：
Locksley, RM
E2a 缺陷的重组腺病毒在棉鼠肺中延长转基因表达。
影响因子：
4.2
作者：
Engelhardt,JF;Litzky,L;Wilson,JM
通讯作者：
Wilson,JM
影响因子：
4.2
作者：
Worgall, S;Wolff, G;Crystal, RG
通讯作者：
Crystal, RG
影响因子：
56.9
作者：
DURIE, FH;FAVA, RA;NOELLE, RJ
通讯作者：
NOELLE, RJ