肿瘤细胞治疗研究
英文原题：Efficient cancer immunogenetherapy by tumor cell lysate modified mRNA formulation.
Efficient cancer immunogenetherapy by tumor cell lysate modified mRNA formulation.
我们的结果证明了TLSV系统在肿瘤免疫基因治疗中的治疗潜力。
基于mRNA的基因治疗在癌症治疗中具有重要作用。人们已投入大量精力研究具有高递送效率的mRNA递送系统，但很少有研究探索递送载体本身的免疫治疗能力。肿瘤细胞裂解物是构建具有免疫刺激潜力的先进mRNA递送系统的理想资源。然而，mRNA载体的有限空间和肿瘤细胞裂解物的复杂组成是其联合功能的障碍。在本研究中，我们提出了一种新型的基于肿瘤细胞裂解物的mRNA递送系统，TLSV/IL-17A（携带白细胞介素（IL）-17A编码mRNA的肿瘤细胞裂解物载体）。TLSV在树突状细胞（DCs）和肿瘤细胞中均表现出高mRNA递送效率。它通过特异性激活浆细胞样树突状细胞（pDCs）和自然杀伤（NK）细胞，触发强大的抗癌免疫应答。通过负载IL-17A mRNA，TLSV/IL-17A有效抑制多种结肠癌模型。我们的结果证明了TLSV系统在肿瘤免疫基因治疗中的治疗潜力。
mRNA-based gene therapy has an important role in cancer therapy. Intensive attention has been paid to investigate mRNA-delivery systems with high efficiency of delivery, but few studies have explored the immunotherapeutic capacity of the delivery vector. A tumor cell lysate represents an ideal resource for constructing advanced mRNA-delivery systems with immunostimulatory potential. However, the limited room of mRNA vectors and the complex composition of the cancer cell lysate are obstacles to their combined function. In this study, we present a novel tumor cell lysate-based mRNA delivery system, TLSV/IL-17A (tumor cell lysate vehicles carrying interleukin (IL)-17A-coded mRNA). TLSV demonstrates high mRNA delivery efficiency in both dendritic cells (DCs) and tumor cells. It triggers a robust anti-cancer immune response by specifically activating plasmacytoid dendritic cells (pDCs) and natural killer (NK) cells. By loading IL-17A mRNA, the TLSV/IL-17A effectively inhibits multiple colon cancer models. Our results demonstrate the therapeutic potential of TLSV system in tumor immunogenetherapy.
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