靶向树突状细胞的肝癌干细胞RNA脂质体疫苗的抗肝癌作用和机制研究

Liver cancer stem cells play a key role in the recurrence and metastasis of liver cancer, and our previous studies have shown that liver cancer stem cells may cure liver cancer. Tumor vaccines use tumor antigens to activate dendritic cells (DCs) and lymphocytes to specifically kill tumors. However, tumor vaccines containing a single tumor antigen have limited antitumor efficacy, and it is difficult to identify specific tumor antigens. Thus, whole tumor cell antigens loaded DC vaccines have better antitumor activity. Compared with tumor cell lysates, DC vaccines containing tumor cell RNA can induce more efficient specific immune responses. Recent studies have shown that DC vaccines containing cancer stem cell antigens have stronger anti-tumor effects. Herein we propose to load the RNA of liver cancer stem cells to the nanoliposomes which have been successfully constructed by us, and modify the liposomes with DC-targeted DEC-205 antibodies, to develop DC-targeted liposome vaccines loaded with the RNA of liver cancer stem cells. This study explores the anti-liver cancer effect and mechanism of the vaccine expected to efficiently target DC and lymphocytes and kill liver cancer stem cells. This study provides novel DC-targeted liposome vaccines loaded with the RNA of liver cancer stem cells, which have important theoretical significance and potential clinical application values in the immunotherapy of liver cancer and other cancers. This is the first study to use nanomedicines to construct cancer stem cell vaccines, providing a new strategy for treatment of liver cancer and other cancers.

肝癌干细胞在肝癌复发转移中扮演关键角色，我们前期研究显示杀伤肝癌干细胞可能治愈肝癌。肿瘤疫苗利用肿瘤抗原激活树突状细胞（DC）和淋巴细胞特异性杀伤肿瘤，载单肿瘤抗原的肿瘤疫苗疗效有限，且特异性肿瘤抗原难以鉴定，因此载全肿瘤细胞抗原的DC疫苗抗肿瘤效果较佳。和肿瘤细胞裂解物相比，载肿瘤细胞RNA的DC疫苗能诱导更高效的特异性免疫应答。最近研究显示载肿瘤干细胞抗原的DC疫苗有更强抗肿瘤作用。我们拟将肝癌干细胞RNA载于我们前期成功构建的纳米脂质体上，在脂质体上修饰DC靶向DEC-205抗体，构建靶向DC的肝癌干细胞RNA脂质体疫苗。本研究对该疫苗抗肝癌作用和机制进行探讨，该疫苗预期能高效靶向激活DC和淋巴细胞并杀伤肝癌干细胞。该研究可提供新型肝癌干细胞RNA脂质体疫苗，对肝癌等肿瘤免疫治疗具有重要理论意义和潜在临床应用价值。该研究首次利用纳米载体构建肿瘤干细胞疫苗，为肝癌等肿瘤治疗提供新策略。

肝癌干细胞在肝癌复发转移中扮演关键角色，与肝癌的生长、复发、转移和耐药相关。我们前期研究显示杀伤肝癌干细胞可能治愈肝癌，可作为今后肝癌诊断和治疗的的靶标。载单肿瘤抗原的肿瘤疫苗疗效有限，且特异性肿瘤抗原难以鉴定，因此我们猜测载肿瘤干细胞抗原的DC疫苗抗肿瘤效果较佳。和肿瘤细胞裂解物相比，载肿瘤细胞RNA的DC疫苗能诱导更高效的特异性免疫应答。在此之前，我们开发了一种靶向脂质体-聚阳离子-DNA(LPD)复合纳米颗粒，该纳米颗粒具有小尺寸、高RNA包封率和优异的血清稳定性。这些颗粒被发现能够成功地将RNA运送到肿瘤部位。我们将肝癌干细胞RNA载于我们前期成功构建的纳米脂质体上，构建靶向DC的肝癌干细胞RNA脂质体疫苗。本研究对该疫苗抗肝癌作用和机制进行探讨，该疫苗能通过基因治疗高效靶向激活DC和淋巴细胞并杀伤肝癌干细胞。该研究可提供新型肝癌干细胞RNA脂质体疫苗，对肝癌等肿瘤免疫治疗具有重要理论意义和潜在临床应用价值，为肝癌等肿瘤治疗提供新思路。