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利用 RNA 干扰提高树突状细胞癌症疫苗效力。

Improving Dendritic Cell Cancer Vaccine Potency Using RNA Interference.

机构信息

Department of Cellular Therapy, Institute for Cancer Research, Oslo University Hospital-Radium, Ullernchausseen, Norway.

Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Ullernchausseen, Norway.

出版信息

Methods Mol Biol. 2020;2115:249-258. doi: 10.1007/978-1-0716-0290-4_14.

Abstract

Dendritic cell cancer vaccines have already become a treatment modality for patients with various cancer types. However, the curative potential of this immunotherapy is limited by the existence of negative feedback mechanisms that control dendritic cells (DCs) and T-cell function. By inhibiting the expression of inhibitory factors using RNA interference technology, a new generation of DC vaccines was developed. Vaccine-stimulated T cells showed antitumor effects both in vitro and in cancer patients. Here, we describe the development and validation of a fully GMP-compliant production process of ex vivo DC cancer vaccines combined with the blockade of immunosuppressive pathways using small interfering RNAs. The protocol can be used for DC-based therapy for all cancer types.

摘要

树突状细胞癌症疫苗已经成为治疗各种癌症类型患者的一种治疗方式。然而,这种免疫疗法的治疗潜力受到控制树突状细胞 (DC) 和 T 细胞功能的负反馈机制的限制。通过使用 RNA 干扰技术抑制抑制因子的表达,开发了新一代的 DC 疫苗。疫苗刺激的 T 细胞在体外和癌症患者中均显示出抗肿瘤作用。在这里,我们描述了一种完全符合 GMP 标准的体外 DC 癌症疫苗生产工艺的开发和验证,该工艺结合了使用小干扰 RNA 阻断免疫抑制途径。该方案可用于所有癌症类型的基于 DC 的治疗。

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