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通过基因调控解锁树突状细胞疫苗的疗效——何时能实现?

Unlocking Dendritic Cell-Based Vaccine Efficacy through Genetic Modulation-How Soon Is Now?

机构信息

Centre for Health and Life Sciences (CHLS), Coventry University, Coventry CV1 5FB, UK.

Department of Biological Sciences, Faculty of Science and Engineering, University of Limerick, V94 T9PX Limerick, Ireland.

出版信息

Genes (Basel). 2023 Nov 23;14(12):2118. doi: 10.3390/genes14122118.

DOI:10.3390/genes14122118
PMID:38136940
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10743214/
Abstract

The dendritic cell (DC) vaccine anti-cancer strategy involves tumour-associated antigen loading and maturation of autologous ex vivo cultured DCs, followed by infusion into the cancer patient. This strategy stemmed from the idea that to induce a robust anti-tumour immune response, it was necessary to bypass the fundamental immunosuppressive mechanisms of the tumour microenvironment that dampen down endogenous innate immune cell activation and enable tumours to evade immune attack. Even though the feasibility and safety of DC vaccines have long been confirmed, clinical response rates remain disappointing. Hence, the full potential of DC vaccines has yet to be reached. Whether this cellular-based vaccination approach will fully realise its position in the immunotherapy arsenal is yet to be determined. Attempts to increase DC vaccine immunogenicity will depend on increasing our understanding of DC biology and the signalling pathways involved in antigen uptake, maturation, migration, and T lymphocyte priming to identify amenable molecular targets to improve DC vaccine performance. This review evaluates various genetic engineering strategies that have been employed to optimise and boost the efficacy of DC vaccines.

摘要

树突状细胞 (DC) 疫苗抗癌策略涉及肿瘤相关抗原负载和自体体外培养的 DC 的成熟,然后输注到癌症患者体内。该策略源于这样一种想法,即要诱导强大的抗肿瘤免疫反应,有必要绕过肿瘤微环境的基本免疫抑制机制,这些机制抑制内源性先天免疫细胞的激活,并使肿瘤能够逃避免疫攻击。尽管 DC 疫苗的可行性和安全性早已得到证实,但临床反应率仍然令人失望。因此,DC 疫苗的全部潜力尚未得到发挥。这种基于细胞的疫苗接种方法是否能完全在免疫治疗武器库中占据一席之地,还有待确定。提高 DC 疫苗免疫原性的尝试将取决于我们对 DC 生物学和参与抗原摄取、成熟、迁移和 T 淋巴细胞启动的信号通路的理解,以确定可改善 DC 疫苗性能的有前途的分子靶点。本综述评估了各种基因工程策略,这些策略已被用于优化和增强 DC 疫苗的功效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb6b/10743214/a16c9d38d0a7/genes-14-02118-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb6b/10743214/416663ab9c06/genes-14-02118-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb6b/10743214/a16c9d38d0a7/genes-14-02118-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb6b/10743214/416663ab9c06/genes-14-02118-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb6b/10743214/a16c9d38d0a7/genes-14-02118-g002.jpg

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Cas9-mediated knockout of Ndrg2 enhances the regenerative potential of dendritic cells for wound healing.Cas9 介导的 Ndrg2 基因敲除增强了树突状细胞的再生潜能,可促进伤口愈合。
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Impaired function of dendritic cells within the tumor microenvironment.
凯林肽与树突状细胞疫苗在4T-1小鼠乳腺癌模型中的协同抗肿瘤作用
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Current Development of Therapeutic Vaccines in Lung Cancer.肺癌治疗性疫苗的当前进展
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New insights for the development of efficient DNA vaccines.为开发高效的 DNA 疫苗提供新的见解。
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Innovative Drug Modalities for the Treatment of Advanced Prostate Cancer.用于治疗晚期前列腺癌的创新药物模式
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