CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
不同大小的噬菌体来源 dsRNA 的免疫调节特性及其作为抗癌疫苗佐剂的应用
英文原题：Immunomodulatory properties of bacteriophage derived dsRNA of different size and their use as anticancer vaccine adjuvants.
查看英文原题
Immunomodulatory properties of bacteriophage derived dsRNA of different size and their use as anticancer vaccine adjuvants.
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中文摘要
基于树突状细胞（DC）的免疫治疗是利用患者免疫系统对抗癌症的策略之一。这种形式的抗癌免疫治疗利用佐剂增强免疫应答，触发固有免疫机制，从而提高免疫治疗效率。在抗癌疫苗生产过程中，用于DC成熟的传统佐剂是细菌LPS。
然而，合成dsRNA也已被证明可刺激固有免疫细胞上的不同受体，并通过toll样受体诱导细胞因子来激活免疫应答。在本研究中，我们探讨了Larifan作为一种天然来源的dsRNA刺激具有促炎（可能具有抗肿瘤）活性的DC成熟的潜力，并比较了不同分子长度Larifan组分之间的这些免疫刺激特性。为了探索该产品用于治疗的适用性，有必要研究其不同组分的特性，并将其与标准佐剂进行比较。
我们通过监测荷瘤小鼠的生存时间，研究了Larifan组分在体内刺激免疫系统的作用。我们还对在体外使用Larifan及其组分与肿瘤抗原共同作用产生的鼠DC进行了表征。与使用LPS成熟的mDC相比，所有Larifan组分均诱导免疫原性标志物CD40、CD80、CD86、CCR7、MHC II的高表达，以及免疫抑制性细胞因子IL-10的较低分泌。未分级dsRNA和短组分FR15的特征在于耐受原性基因Ido1表达最低，而免疫原性基因Clec7a、Tnf、Icosl、Il12rb2、Cd209a表达最高。在小鼠模型中，使用中等长度FR9和FR15处理的小鼠观察到最佳的总生存率。
我们可以说，Larifan及其各组分在刺激成熟DC的表型和功能活性方面均优于LPS作为疫苗佐剂。利用这些因子使DC成熟，可诱导有价值的抗癌免疫应答。
展开英文摘要原文
Dendritic cell (DC) based immunotherapy is one of the strategies to combat cancer invoking a patient's immune system. This form of anticancer immunotherapy employs adjuvants to enhance the immune response, triggering mechanisms of innate immunity and thus increase immunotherapeutic efficiency. A conventional adjuvant for DCs maturation during production of anticancer vaccines is bacterial LPS. Nevertheless, synthetic dsRNAs were also shown to stimulate different receptors on innate immune cells and to activate immune responses through induction of cytokines via toll-like receptors.
In our study we investigated the potential of Larifan as dsRNA of natural origin to stimulate maturation of DCs with proinflammatory (possible antitumoral) activity and to compare these immunostimulatory properties between Larifan's fractions with different molecular lengths. To explore the suitability of this product for therapy, it is necessary to study the properties of its different fractions and compare them to standard adjuvants.
We investigated the effect of Larifan's fractions on immune system stimulation in vivo by monitoring the survival time of tumor-bearing mice. Murine DCs produced in vitro using Larifan and its fractions together with tumor antigens during production were also characterized. All Larifan fractions resulted in inducing high expression of immunogenic markers CD40, CD80, CD86, CCR7, MHC II and lower secretion of the immunosuppressive cytokine IL-10, compared to the maturation with LPS in mDCs.
The lowest expression of tolerogenic gene Ido1 and highest expression of the immunogenic genes Clec7a, Tnf, Icosl, Il12rb2, Cd209a were characteristic to the unfractionated dsRNA and short fraction FR15. In the mouse model the best overall survival rate was observed in mice treated with medium-length FR9 and FR15.
We can state that both Larifan and its fractions were superior to LPS as vaccine adjuvants in stimulating phenotype and functional activity of mature DCs. DCs maturation using these factors induces a valuable anticancer immune response.
论文信息
- 作者
- Dobrovolskienė N、Balevičius R、Mlynska A、Žilionytė K、Aleksander Krasko J、Strioga M、Lieknina I、Pjanova D
- 第一作者单位
- Laboratory of Immunology, National Cancer Institute, Santariškių g. 1, LT-08660 Vilnius, Lithuania. Electronic address: neringa.dobrovolskiene@nvi.lt.United States
- 通讯作者单位
- Laboratory of Immunology, National Cancer Institute, Santariškių g. 1, LT-08660 Vilnius, Lithuania; Department of Chemistry and Bioengineering, Vilnius Gediminas Technical University, Saulėtekio al. 11, LT-10223 Vilnius, Lithuania. Electronic address: vita.pasukoniene@nvi.lt.United States
- 文献类型
- 非美国政府资助研究
- 期刊
- Vaccine2024 Jan 25
- 原文标识
- PubMed 38184395 · DOI 10.1016/j.vaccine.2023.12.071