Dendritic cell (DC)-based tumor vaccines are a promising immunotherapeutic method of cancer treatment. However, their therapeutic applications are significantly limited by their weak immunogenicity, costly culturing steps, and easily degradable properties. Thus, the anti-tumor activity for the vaccines should be improved. In this study, a novel lipid nanoparticle (M/CpG-ODN-H22-Lipo) was developed, which was conjugated with synthetic CpG oligodeoxynucleotides (CpG-ODN) and mannose and then loaded with H22 hepatoma lysate. Our data corroborate that M/CpG-ODN-H22-Lipo selectively targeted DCs and significantly increased their induced-maturation. Besides, the vaccine halted tumor growth and extended survival of mice with hepatocellular carcinoma. Moreover, M/CpG-ODN-H22-Lipo treatment reduced the percentages of myeloid-derived suppressor cells (in the tumor and bone marrow) and regulatory T cells (Treg) in the spleen. In contrast, the number of IFN-gamma-positive cells in the spleen along with the serum IgG levels were up-regulated. Moreover, tumor angiogenesis and tumor-cell proliferation were halted by the treatment of M/CpG-ODN-H22-Lipo, whereas tumor cell apoptosis was up-regulated. Our data revealed that CD8 + T cells and NK cells were vital to mediate the anti-tumor immunity of M/CpG-ODN-H22-Lipo treatment. In sum, the results here proved M/CpG-ODN-H22-Lipo vaccine a safe, specific and effective DC-based anti-tumor immunotherapy with great potential for clinical applications.

中文翻译：

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甘露糖-CpG-寡脱氧核苷酸缀合和肝癌裂解液加载的纳米脂质体的抗肿瘤活性，用于体内靶向树突状细胞。

基于树突细胞（DC）的肿瘤疫苗是一种有前途的免疫疗法，用于治疗癌症。然而，它们的治疗应用由于其弱的免疫原性，昂贵的培养步骤和易于降解的特性而受到极大的限制。因此，应提高疫苗的抗肿瘤活性。在这项研究中，开发了一种新型脂质纳米颗粒（M / CpG-ODN-H22-Lipo），将其与合成的CpG寡脱氧核苷酸（CpG-ODN）和甘露糖偶联，然后装载了H22肝癌裂解物。我们的数据证实了M / CpG-ODN-H22-Lipo选择性靶向DC，并显着增加了其诱导成熟。此外，该疫苗阻止了肝细胞癌小鼠的肿瘤生长并延长了其生存期。此外，M / CpG-ODN-H22-Lipo治疗降低了脾脏中髓样来源的抑制细胞（在肿瘤和骨髓中）和调节性T细胞（Treg）的百分比。相比之下，IFN-脾中的γ-阳性细胞与血清IgG水平一起被上调。此外，通过治疗M / CpG-ODN-H22-Lipo可阻止肿瘤血管生成和肿瘤细胞增殖，而肿瘤细胞凋亡则被上调。我们的数据显示，CD8 + T细胞和NK细胞对于介导M / CpG-ODN-H22-Lipo治疗的抗肿瘤免疫至关重要。总而言之，这里的结果证明了M / CpG-ODN-H22-Lipo疫苗是一种安全，特异性和有效的基于DC的抗肿瘤免疫疗法，具有很大的临床应用潜力。