关键词: adjuvants cancer immunotherapy endogenous fumarate ligands ferric ions metal organic framework nanotechnology personalized cancer vaccines

Mesh : Animals Mice Cancer Vaccines Metal-Organic Frameworks Autoantigens Iron Antigens, Neoplasm Neoplasms / therapy

来  源:   DOI:10.3389/fimmu.2023.1328379   PDF(Pubmed)

Abstract:
Considering the diversity of tumors, it is of great significance to develop a simple, effective, and low-cost method to prepare personalized cancer vaccines.
In this study, a facile one-pot synthetic route was developed to prepare cancer vaccines using model antigen or autologous tumor antigens based on the coordination interaction between Fe3+ ions and endogenous fumarate ligands.
Herein, Fe-based metal organic framework can effectively encapsulate tumor antigens with high loading efficiency more than 80%, and act as both delivery system and adjuvants for tumor antigens. By adjusting the synthesis parameters, the obtained cancer vaccines are easily tailored from microscale rod-like morphology with lengths of about 0.8 μm (OVA-ML) to nanoscale morphology with sizes of about 50~80 nm (OVA-MS). When cocultured with antigen-presenting cells, nanoscale cancer vaccines more effectively enhance antigen uptake and Th1 cytokine secretion than microscale ones. Nanoscale cancer vaccines (OVA-MS, dLLC-MS) more effectively enhance lymph node targeting and cross-presentation of tumor antigens, mount antitumor immunity, and inhibit the growth of established tumor in tumor-bearing mice, compared with microscale cancer vaccines (OVA-ML, dLLC-ML) and free tumor antigens.
Our work paves the ways for a facile, rapid, and low-cost preparation approach for personalized cancer vaccines.
摘要:
考虑到肿瘤的多样性,开发一个简单的,有效,和低成本的方法来制备个性化的癌症疫苗。
在这项研究中,基于Fe3+离子和内源性延胡索酸配体之间的配位相互作用,开发了使用模型抗原或自体肿瘤抗原制备癌症疫苗的简易一锅法合成途径.
这里,Fe基金属有机框架能有效包裹肿瘤抗原,高加载效率达80%以上,并充当肿瘤抗原的递送系统和佐剂。通过调整合成参数,所获得的癌症疫苗很容易从长度约为0.8μm的微尺度棒状形态(OVA-ML)调整到尺寸约为50~80nm的纳米级形态(OVA-MS)。当与抗原呈递细胞共培养时,纳米癌症疫苗比微米级疫苗更有效地增强抗原摄取和Th1细胞因子分泌。纳米癌症疫苗(OVA-MS,dLLC-MS)更有效地增强淋巴结靶向和肿瘤抗原的交叉呈递,提高抗肿瘤免疫力,并抑制荷瘤小鼠中已建立的肿瘤的生长,与微型癌症疫苗(OVA-ML,dLLC-ML)和游离肿瘤抗原。
我们的工作为轻松,快速,以及个性化癌症疫苗的低成本制备方法。
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