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一种 iPSC 衍生的外泌体脉冲树突状细胞疫苗可增强黑色素瘤的抗肿瘤免疫

英文原题:An iPSC-derived exosome-pulsed dendritic cell vaccine boosts antitumor immunity in melanoma.

查看英文原题

An iPSC-derived exosome-pulsed dendritic cell vaccine boosts antitumor immunity in melanoma.

PubMed 2023/06/12(内容时间) Mol Ther Q1 · IF 11.4(JCR 2025)

研究概要

诱导多能干细胞(iPSCs)表达广谱的肿瘤相关抗原,并对多种肿瘤发挥预防作用。

中文摘要

诱导多能干细胞(iPSCs)表达广谱的肿瘤相关抗原,并对多种肿瘤发挥预防作用。然而,仍存在一些问题,如潜在的致瘤性、转运至淋巴结和脾脏的困难以及抗肿瘤效果有限。因此,设计一种安全有效的基于iPSC的肿瘤疫苗是必要的。我们制备了iPSC来源的外泌体,并将其与DC(树突状细胞)孵育以进行脉冲,从而探索其在小鼠黑色素瘤模型中的抗肿瘤效果。我们在体外和体内评估了由iPSC外泌体脉冲的DC疫苗(DC + EXO)所诱导的抗肿瘤免疫反应。在DC + EXO疫苗接种后,提取的脾T细胞在体外有效杀伤了多种肿瘤细胞(黑色素瘤、肺癌、乳腺癌和结直肠癌)。此外,DC + EXO疫苗接种显著抑制了小鼠模型中的黑色素瘤生长和肺转移。进一步,DC + EXO疫苗接种诱导了长期T细胞反应并防止了黑色素瘤再攻击。最后,生物相容性研究表明,该DC疫苗未显著改变正常细胞和小鼠内脏的活力。因此,我们的研究可能为临床使用提供一种安全有效的基于iPSC的肿瘤疫苗的前瞻性策略。

展开英文摘要原文

Induced pluripotent stem cells (iPSCs) express a broad spectrum of tumor-associated antigens and exert prophylactic effects on various tumors. However, some problems remain, such as potential tumorigenicity, challenges in transport to the lymph nodes and spleen, and limited antitumor effects. Thus, designing a safe and effective iPSC-based tumor vaccine is necessary. We prepared iPSC-derived exosomes and incubated them with DCs (dendritic cells) for pulsing to explore their antitumor effects in murine melanoma models. The antitumor immune response induced by the DC vaccine pulsed with iPSC exosomes (DC + EXO) was assessed in vitro and in vivo. After DC + EXO vaccination, extracted spleen T cells effectively killed a variety of tumor cells (melanoma, lung cancer, breast cancer, and colorectal cancer) in vitro. In addition, DC + EXO vaccination significantly inhibited melanoma growth and lung metastasis in mouse models. Furthermore, DC + EXO vaccination induced long-term T cell responses and prevented melanoma rechallenge. Finally, biocompatibility studies showed that the DC vaccine did not significantly alter the viability of normal cells and mouse viscera. Hence, our research may provide a prospective strategy of a safe and effective iPSC-based tumor vaccine for clinical use.

论文信息

作者
Wang R、Zhu T、Hou B、Huang X
第一作者单位
Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong, China; Department of Gastrointestinal Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong, China.China
通讯作者单位
Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong, China; Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai 519000, Guangdong, China. Electronic address: huangxi6@mail.sysu.edu.cn.China
文献类型
非美国政府资助研究
期刊
Molecular therapy : the journal of the American Society of Gene Therapy2023 Aug 2
原文标识
PubMed 37312452 · DOI 10.1016/j.ymthe.2023.06.005