不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel：ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
利用 DNA 折纸技术精细调控 CpG 空间分布以改善癌症疫苗接种
英文原题：Fine tuning of CpG spatial distribution with DNA origami for improved cancer vaccination.
查看英文原题
Fine tuning of CpG spatial distribution with DNA origami for improved cancer vaccination.
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中文摘要
多价配体呈递通常增强受体激活和下游信号传导。DNA折纸术可精确控制配体的纳米级间距，这是治疗性纳米颗粒的一个潜在有用特征。在此，我们使用方形块DNA折纸平台来探究CpG寡核苷酸间距的重要性。CpG与Toll样受体结合，因此具有激活树突状细胞的作用。通过体外细胞培养研究和体内肿瘤治疗模型，我们证明当CpG间距为3.5 nm时，方形块诱导Th1免疫极化。我们观察到这种DNA折纸疫苗增强DC激活、抗原交叉呈递、CD8 T细胞激活、Th1极化的CD4激活和NK 细胞激活。该疫苗还在黑色素瘤和淋巴瘤模型中与抗PD-L1有效协同以改善癌症免疫治疗，并诱导长期T细胞记忆。我们的结果表明，DNA折纸术可作为控制佐剂间距和共递送抗原的疫苗平台。
展开英文摘要原文
Multivalent presentation of ligands often enhances receptor activation and downstream signalling. DNA origami offers a precise nanoscale spacing of ligands, a potentially useful feature for therapeutic nanoparticles.
Here we use a square-block DNA origami platform to explore the importance of the spacing of CpG oligonucleotides. CpG engages Toll-like receptors and therefore acts to activate dendritic cells. Through in vitro cell culture studies and in vivo tumour treatment models, we demonstrate that square blocks induce Th1 immune polarization when CpG is spaced at 3. 5 nm.
We observe that this DNA origami vaccine enhances DC activation, antigen cross-presentation, CD8 T-cell activation, Th1-polarized CD4 activation and natural-killer-cell activation. The vaccine also effectively synergizes with anti-PD-L1 for improved cancer immunotherapy in melanoma and lymphoma models and induces long-term T-cell memory.
Our results suggest that DNA origami may serve as a platform for controlling adjuvant spacing and co-delivering antigens in vaccines.
论文信息
- 作者
- Zeng YC、Young OJ、Wintersinger CM、Anastassacos FM、MacDonald JI、Isinelli G、Dellacherie MO、Sobral M
- 第一作者单位
- Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.United States
- 通讯作者单位
- Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. william_shih@dfci.harvard.edu.United States
- 期刊
- Nature nanotechnology2024 Jul
- 原文标识
- PubMed 38491184 · DOI 10.1038/s41565-024-01615-3