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树突状细胞衍生的外泌体(Dex)作为一种抗癌纳米疫苗的最新进展。

Recent progress of dendritic cell-derived exosomes (Dex) as an anti-cancer nanovaccine.

机构信息

Department of Hematology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, No. 32, West Section 2, First Ring Road, Qingyang District, Chengdu 610000, China.

出版信息

Biomed Pharmacother. 2022 Aug;152:113250. doi: 10.1016/j.biopha.2022.113250. Epub 2022 Jun 13.

Abstract

Although cancer vaccines such as dendritic cell (DC) vaccines and peptide vaccines have become appealing and attractive anticancer immunotherapy options in recent decades, some obstacles have hindered their successful application in the clinical setting. The difficulties associated with the high cost of DC preparation, storage of DC vaccines, tumor-mediated immunosuppressive environment, identification of specific tumor antigens, and high degradation of antigen peptides in vivo limit the clinical application and affect the outcomes of these cancer vaccines. Recently, nanocarriers have been considered as a new approach for vaccine delivery. As biogenic nanocarriers, exosomes are small membrane vesicles secreted by cells that carry various proteins, RNAs, and lipids. More importantly, DC-derived exosomes (Dex) express tumor antigens, MHC molecules, and co-stimulatory molecules on their surface, which trigger the release of antigen-specific CD4 and CD8 T cells. With their membrane structure, Dex can avoid high degradation while ensuring favorable biocompatibility and biosafety in vivo. In addition, Dex can be stored in vitro for a longer period, which facilitates a significant reduction in production costs. Furthermore, they have shown better antitumor efficacy in preclinical studies compared with DC vaccines owing to their higher immunogenicity and stronger resistance to immunosuppressive effects. However, the clinical efficacy of Dex vaccines remains limited. In this review, we aimed to evaluate the efficacy of Dex as an anticancer nanovaccine.

摘要

虽然树突状细胞 (DC) 疫苗和肽疫苗等癌症疫苗已成为近几十年来有吸引力的抗癌免疫治疗选择,但一些障碍阻碍了它们在临床环境中的成功应用。DC 制备成本高、DC 疫苗储存、肿瘤介导的免疫抑制环境、特定肿瘤抗原的识别以及抗原肽在体内的高降解等困难限制了这些癌症疫苗的临床应用并影响了其效果。最近,纳米载体被认为是疫苗传递的一种新方法。作为生物源纳米载体,外泌体是细胞分泌的小膜囊泡,携带各种蛋白质、RNA 和脂质。更重要的是,树突状细胞来源的外泌体 (Dex) 在其表面表达肿瘤抗原、MHC 分子和共刺激分子,触发抗原特异性 CD4 和 CD8 T 细胞的释放。凭借其膜结构,Dex 可以避免高降解,同时确保体内良好的生物相容性和生物安全性。此外,Dex 可以在体外储存更长时间,这大大降低了生产成本。此外,由于其更高的免疫原性和更强的抗免疫抑制作用,与 DC 疫苗相比,它们在临床前研究中显示出更好的抗肿瘤疗效。然而,Dex 疫苗的临床疗效仍然有限。在这篇综述中,我们旨在评估 Dex 作为抗癌纳米疫苗的疗效。

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