Department of Hematology, Oslo University Hospital-Rikshospitalet, Oslo, Norway.
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.
Methods Mol Biol. 2020;2115:281-287. doi: 10.1007/978-1-0716-0290-4_16.
When introduced into endosomes via cationic lipids, certain small interfering RNA (siRNA) sequences activate the interferon signaling pathways in immune cells such as dendritic cells (DCs), known as the most efficient antigen-presenting cells of the immune system. Human immature DCs produced high levels of the immune-response protein interferon-α and tumor necrosis factor- α upon incubation with siRNA/lipid formulations, resulting in their maturation and expression of co-stimulatory molecules like CD80, CD86, and CD40 on the cell surface. These molecules are used by mature DCs to co-stimulate T cells during antigen presentation in lymphoid organs. Ex vivo loading of immature DCs with DOTAP-formulated immunostimulatory siRNAs and tumor antigens has proven effective as a cancer vaccine in a rat model of acute myeloid leukemia. Here, we describe this new vaccination strategy that targets tumor cells by activating DCs and blocking the expression of immunosuppressive factors.
当通过阳离子脂质体导入内体时，某些小干扰 RNA（siRNA）序列会激活免疫细胞（如树突状细胞（DC））中的干扰素信号通路，DC 是免疫系统中最有效的抗原呈递细胞。在与 siRNA/脂质体制剂孵育时，人类未成熟的 DC 会产生高水平的免疫反应蛋白干扰素-α和肿瘤坏死因子-α，导致其成熟，并在细胞表面表达共刺激分子，如 CD80、CD86 和 CD40。这些分子被成熟的 DC 用于在淋巴器官中呈递抗原时共同刺激 T 细胞。在急性髓细胞性白血病的大鼠模型中，已证明用 DOTAP 制剂的免疫刺激性 siRNA 和肿瘤抗原体外加载未成熟的 DC 作为癌症疫苗是有效的。在这里，我们描述了这种通过激活 DC 并阻断免疫抑制因子表达来靶向肿瘤细胞的新疫苗接种策略。
