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用于癌症治疗的基因修饰树突状细胞疫苗

Gene-modified dendritic cell vaccines for cancer.

作者信息

Abraham Rebecca S, Mitchell Duane A

机构信息

UF Brain Tumor Immunotherapy Program, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Department of Neurosurgery, University of Florida, Gainesville, FL 32605.

UF Brain Tumor Immunotherapy Program, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Department of Neurosurgery, University of Florida, Gainesville, FL 32605.

出版信息

Cytotherapy. 2016 Nov;18(11):1446-1455. doi: 10.1016/j.jcyt.2016.09.009.

Abstract

Dendritic cell (DC) vaccines are an immunotherapeutic approach to cancer treatment that use the antigen-presentation machinery of DCs to activate an endogenous anti-tumor response. In this treatment strategy, DCs are cultured ex vivo, exposed to tumor antigens and administered to the patient. The ex vivo culturing provides a unique and powerful opportunity to modify and enhance the DCs. As such, a variety of genetic engineering approaches have been employed to optimize DC vaccines, including the introduction of messenger RNA and small interfering RNA, viral gene transduction, and even fusion with whole tumor cells. In general, these modifications aim to improve targeting, enhance immunogenicity, and reduce susceptibility to the immunosuppressive tumor microenvironment. It has been demonstrated that several of these modifications can be employed in tandem, allowing for fine-tuning and optimization of the DC vaccine across multiple metrics. Thus, the application of genetic engineering techniques to the dendritic cell vaccine platform has the potential to greatly enhance its efficacy in the clinic.

摘要

树突状细胞(DC)疫苗是一种癌症治疗的免疫治疗方法,它利用树突状细胞的抗原呈递机制来激活内源性抗肿瘤反应。在这种治疗策略中,树突状细胞在体外培养,接触肿瘤抗原后再给予患者。体外培养为修饰和增强树突状细胞提供了独特而强大的机会。因此,人们采用了多种基因工程方法来优化DC疫苗,包括引入信使核糖核酸和小干扰核糖核酸、病毒基因转导,甚至与完整肿瘤细胞融合。一般来说,这些修饰旨在改善靶向性、增强免疫原性,并降低对免疫抑制性肿瘤微环境的敏感性。已经证明,其中几种修饰可以串联使用,从而能够在多个指标上对DC疫苗进行微调优化。因此,将基因工程技术应用于树突状细胞疫苗平台有可能极大地提高其临床疗效。

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