Department of Urologic Surgery, University of Minnesota Medical School, 420 Delaware Street SE, Minneapolis, MN, USA.
J Interferon Cytokine Res. 2009 Nov;29(11):719-28. doi: 10.1089/jir.2008.0073.
Long-term treatment of mouse cancer cells with interferon-alpha (IFN-alpha) converts parental B16 melanoma cells to B16alpha vaccine cells. Inoculation of syngeneic mice with UV-irradiated B16alpha vaccine cells triggers immunity to the parental B16 tumor that is mediated by host macrophages, T cells, and NK cells. Lymph node cells from mice inoculated with irradiated B16alpha vaccine cells, but not with irradiated parental cells, proliferate when cultured in vitro, suggesting long-term in vivo activation of lymphoid cells. Both IL-15 mRNA and IL-15 protein are highly induced in B16alpha vaccine cells. The bulk of the induced IL-15 is shown to be cell-associated, either cytoplasmic or membranous. The current study investigated the feasibility of applying the B16alpha vaccination protocol to generate a cancer vaccine against murine RM-1 prostate carcinoma. In comparison to B16alpha vaccine cells, long-term IFN-alpha-treated RM-1 cells (RM-1alpha vaccine cells) showed significant IL-15 mRNA induction but relatively low IL-15 protein up-regulation. When UV-irradiated, a 3-fold increase in intracellular IL-15 was observed in RM-1alpha vaccine cells, suggesting UV damage may have negated a possible control mechanism for IL-15 synthesis. Efficacy of in vivo vaccination of syngeneic mice with UV-irradiated RM-1alpha and B16alpha vaccine cells showed correlation between high IL-15 level and high vaccine efficacy in B16alpha cells compared to low IL-15 level and low vaccine efficacy in RM-1alpha cells. This supports the concept that the induction of IL-15 in tumor cells can be useful for creating whole-cell cancer vaccines.
长期用干扰素-α（IFN-α）处理鼠癌细胞可将亲本 B16 黑素瘤细胞转化为 B16α疫苗细胞。用紫外线照射的 B16α疫苗细胞接种同基因小鼠可引发对亲本 B16 肿瘤的免疫，这种免疫是由宿主巨噬细胞、T 细胞和 NK 细胞介导的。用紫外线照射的 B16α疫苗细胞而非亲本细胞接种的小鼠的淋巴结细胞在体外培养时增殖，提示淋巴样细胞在体内长期激活。B16α疫苗细胞中高度诱导了 IL-15 mRNA 和 IL-15 蛋白。大量诱导的 IL-15 被证明与细胞相关，存在于细胞质或膜上。本研究探讨了应用 B16α疫苗接种方案来生成针对鼠 RM-1 前列腺癌的癌症疫苗的可行性。与 B16α疫苗细胞相比，长期 IFN-α处理的 RM-1 细胞（RM-1α疫苗细胞）显示出明显的 IL-15 mRNA 诱导，但 IL-15 蛋白的上调相对较低。当用紫外线照射时，RM-1α疫苗细胞中的细胞内 IL-15 增加了 3 倍，这表明紫外线损伤可能消除了 IL-15 合成的可能控制机制。用紫外线照射的 RM-1α和 B16α疫苗细胞对同基因小鼠进行体内接种的功效表明，与 RM-1α细胞中低 IL-15 水平和低疫苗功效相比，B16α细胞中高 IL-15 水平与高疫苗功效之间存在相关性。这支持了这样的概念，即肿瘤细胞中 IL-15 的诱导可用于创建全细胞癌症疫苗。
