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基于治疗性树突状细胞的癌症疫苗:现状

Therapeutic dendritic cell-based cancer vaccines: the state of the art.

作者信息

Strioga Marius M, Felzmann Thomas, Powell Daniel J, Ostapenko Valerijus, Dobrovolskiene Neringa T, Matuskova Miroslava, Michalek Jaroslav, Schijns Virgil E J

机构信息

Department of Immunology, Center of Oncosurgery, Institute of Oncology, Vilnius University, Vilnius, Lithuania.

出版信息

Crit Rev Immunol. 2013;33(6):489-547. doi: 10.1615/critrevimmunol.2013008033.

DOI:10.1615/critrevimmunol.2013008033
PMID:24266347
Abstract

Dendritic cells (DCs) are the most potent professional antigen-presenting cells, capable of initiating proper adaptive immune responses. Although tumor-infiltrating DCs are able to recognize cancer cells and uptake tumor antigens, they often have impaired functions because of the immunosuppressive tumor milieu. Therefore, DCs are targeted by therapeutic means either in vivo or ex vivo to facilitate tumor antigen presentation to T cells and induce or promote efficient antitumor immune responses in cancer patients. This immunotherapeutical approach is defined as specific active tumor immunotherapy or therapeutic cancer vaccination. In this review we briefly discuss general aspects of DC biology, followed by a thorough description of the current knowledge and optimization trends of DC vaccine production ex vivo, including various approaches for the induction of proper DC maturation and efficient loading with tumor antigens. We also discuss critical clinical aspects of DC vaccine application in cancer patients, including protocols of administration (routes and regimens), individualization of tumor immunotherapy, prediction and proper evaluation of immune and clinical responses to immunotherapy, and the critical role of combining tumor immunotherapy with other cancer treatment strategies to achieve maximal therapeutic effects.

摘要

树突状细胞(DCs)是最强大的专职抗原呈递细胞,能够启动适当的适应性免疫反应。尽管肿瘤浸润性DCs能够识别癌细胞并摄取肿瘤抗原,但由于免疫抑制性肿瘤微环境,它们的功能常常受损。因此,通过体内或体外治疗手段靶向DCs,以促进肿瘤抗原呈递给T细胞,并在癌症患者中诱导或促进有效的抗肿瘤免疫反应。这种免疫治疗方法被定义为特异性主动肿瘤免疫治疗或治疗性癌症疫苗接种。在本综述中,我们简要讨论DC生物学的一般方面,随后详细描述目前体外DC疫苗生产的知识和优化趋势,包括诱导DC适当成熟和有效负载肿瘤抗原的各种方法。我们还讨论了DC疫苗在癌症患者中应用的关键临床方面,包括给药方案(途径和疗程)、肿瘤免疫治疗的个体化、对免疫治疗的免疫和临床反应的预测和适当评估,以及将肿瘤免疫治疗与其他癌症治疗策略相结合以实现最大治疗效果的关键作用。

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