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RNA 脉冲树突状细胞:癌症免疫治疗的一种方法。

RNA pulsed dendritic cells: an approach for cancer immunotherapy.

机构信息

Drug Delivery Research Group, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160 014, Chandigarh, India.

出版信息

Vaccine. 2013 Feb 6;31(8):1141-56. doi: 10.1016/j.vaccine.2012.12.027. Epub 2013 Jan 8.

Abstract

The immunotherapy of cancer is aimed at evoking both branches of immune system to elicite specific immune responses directed against tumor antigens to deal with residual tumor cells upon interaction, and thereby decreases mortality as well as morbidity of cancer patients. As dendritic cells (DCs) are specialized for antigen presentation, and their immunogenicity leads to the induction of antigen specific immune responses, various immunotherapeutic approaches have been designed for using DCs to present tumor-associated antigens to T-lymphocytes. As a part of proposed strategy ex vivo generated DCs might be loaded with antigens and re-infused to the patients and/or they can be used for the ex vivo expansion of anti-tumor lymphocytes. The DCs loaded ex vivo with RNA can be safely administered which proves to be an asset for producing antigen specific immune responses. Furthermore, already conducted studies have prompted clinical trials to be designed to investigate immunological and clinical effects of RNA pulsed DCs administered as an engineered therapeutic vaccine in cancer patients. However, selection of the antigens of interest, methods for introducing TAAgs into MHC class I and II processing pathways, methods for isolation and activation of DCs, and route of administration are the parameters to be considered for designing and conducting clinical trials with engineered DCs. The enhanced RNA transfection efficiency would further improve antigen processing and presentation and T-cell co-stimulation, resulting in the induction of heightened anti-tumor immune responses. Therefore, RNA transfected dendritic cells continue to hold promise for cellular immunotherapy and opens new avenues to devising further strategies for cancer therapeutic interventions.

摘要

癌症的免疫疗法旨在激发免疫系统的两个分支,以引发针对肿瘤抗原的特异性免疫反应,以应对相互作用后的残留肿瘤细胞,从而降低癌症患者的死亡率和发病率。树突状细胞 (DC) 专门用于抗原呈递,其免疫原性导致诱导针对抗原的特异性免疫反应,因此已经设计了各种免疫治疗方法来利用 DC 将肿瘤相关抗原呈递给 T 淋巴细胞。作为提出的策略的一部分,体外生成的 DC 可以负载抗原并重新注入患者体内,和/或用于体外扩增抗肿瘤淋巴细胞。负载 RNA 的 DC 可以安全地给药,这证明了其在产生抗原特异性免疫反应方面的优势。此外,已经进行的研究促使设计临床试验,以研究作为工程治疗性疫苗在癌症患者中给予 RNA 脉冲 DC 的免疫和临床效果。然而,选择感兴趣的抗原、将 TAAg 引入 MHC Ⅰ类和Ⅱ类加工途径的方法、DC 的分离和激活方法以及给药途径是设计和进行工程化 DC 临床试验时需要考虑的参数。增强的 RNA 转染效率将进一步改善抗原加工和呈递以及 T 细胞共刺激,从而诱导增强的抗肿瘤免疫反应。因此,转染 RNA 的树突状细胞继续为细胞免疫疗法带来希望,并为癌症治疗干预措施开辟了新的途径。

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