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树突状细胞疫苗接种在癌症治疗中的临床应用

Clinical applications of dendritic cell vaccination in the treatment of cancer.

作者信息

Cranmer Lee D, Trevor Katrina T, Hersh Evan M

机构信息

Department of Hematology and Oncology, The Arizona Cancer Center, University of Arizona/University Medical Center, 1515 N. Campbell Ave., Tucson, AZ 85724, USA.

出版信息

Cancer Immunol Immunother. 2004 Apr;53(4):275-306. doi: 10.1007/s00262-003-0432-5. Epub 2003 Nov 26.

DOI:10.1007/s00262-003-0432-5
PMID:14648069
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11032969/
Abstract

Dendritic cell (DC) immunotherapy has shown significant promise in animal studies as a potential treatment for cancer. Its application in the clinic depends on the results of human trials. Here, we review the published clinical trials of cancer immunotherapy using exogenously antigen-exposed DCs. We begin with a short review of general properties and considerations in the design of such vaccines. We then review trials by disease type. Despite great efforts on the part of individual investigative groups, most trials to date have not yielded data from which firm conclusions can be drawn. The reasons for this include nonstandard DC preparation and vaccination protocols, use of different antigen preparations, variable means of immune assessment, and nonrigorous criteria for defining clinical response. While extensive animal studies have been conducted using DCs, optimal parameters in humans remain to be established. Unanswered questions include optimal cell dose, use of mature versus immature DCs for vaccination, optimal antigen preparation, optimal route, and optimal means of assessing immune response. It is critical that these questions be answered, as DC therapy is labor- and resource-intensive. Cooperation is needed on the part of the many investigators in the field to address these issues. If such cooperation is not forthcoming, the critical studies that will be required to make DC therapy a clinically and commercially viable enterprise will not take place, and this therapy, so promising in preclinical studies, will not be able to compete with the many other new approaches to cancer therapy presently in development. Trials published in print through June 2003 are included. We exclude single case reports, except where relevant, and trials with so many variables as to prevent interpretation about DC therapy effects.

摘要

树突状细胞(DC)免疫疗法在动物研究中已显示出作为癌症潜在治疗方法的巨大前景。其在临床上的应用取决于人体试验的结果。在此,我们综述了使用外源性抗原暴露的DC进行癌症免疫治疗的已发表临床试验。我们首先简要回顾此类疫苗设计中的一般特性和注意事项。然后按疾病类型综述试验。尽管各个研究小组付出了巨大努力,但迄今为止大多数试验尚未得出能得出确凿结论的数据。原因包括DC制备和接种方案不标准、使用不同的抗原制剂、免疫评估方法多样以及定义临床反应的标准不严格。虽然已经使用DC进行了广泛的动物研究,但人类的最佳参数仍有待确定。未解决的问题包括最佳细胞剂量、用于接种的成熟与未成熟DC的使用、最佳抗原制剂、最佳途径以及评估免疫反应的最佳方法。回答这些问题至关重要,因为DC疗法耗费人力和资源。该领域的众多研究人员需要合作来解决这些问题。如果没有这种合作,使DC疗法成为临床和商业上可行的企业所需的关键研究将无法进行,而这种在临床前研究中前景广阔的疗法将无法与目前正在开发的许多其他癌症治疗新方法竞争。纳入了截至2003年6月发表的试验。我们排除单个病例报告,除非相关,以及变量过多以至于无法解读DC治疗效果的试验。

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