Development of a therapy against metastatic bladder cancer using an interleukin-2 surface-modified MB49 bladder cancer stem cells vaccine.
Development of a therapy against metastatic bladder cancer using an interleukin-2 surface-modified MB49 bladder cancer stem cells vaccine.
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使用白细胞介素 2 表面修饰的 MB49 膀胱癌干细胞疫苗开发针对转移性膀胱癌的疗法
DOI：
10.1186/s13287-015-0211-1
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发表时间：
2015-11-14
影响因子：
7.5
通讯作者：
Tan WL
中科院分区：
文献类型：
--
作者：
Zhu YT;Pang SY;Lei CY;Luo Y;Chu QJ;Tan WL
在先前的研究中，链霉亲和素白细胞介素-2（SA-IL-2）修饰的MB 49疫苗在小鼠模型中对膀胱癌有效。然而，一小部分肿瘤重新生长，因为疫苗不能消除MB 49膀胱癌干细胞（MCSC）。因此，我们开发了SA-IL-2修饰的MCSCs疫苗，并评估了其抗肿瘤作用。MCSCs具有肿瘤干细胞（cancer stem cells，CSCs）的特征，具有高表达CSCs标志物、较高的化疗抗性、较大的体外迁移性和较强的体内致瘤性。制备SA-IL-2 MCSCs疫苗，并对其生物学活性进行评价。通过动物实验，观察疫苗的保护性、治疗性、特异性和记忆性免疫应答，以确定疫苗是否能引起抗肿瘤免疫，并对转移性膀胱癌有作用。MCSCs表达CD 133和CD 44水平较高，对化疗敏感性较低，迁移能力较强，致瘤能力较强。成功制备的SA-IL-2 MCSCs疫苗在动物实验中抑制肿瘤体积并延长小鼠存活时间。实验组IgG的表达、树突状细胞、CD 8+和CD 4 + T细胞的数量均高于4个对照组。SA-IL-2 MCSC疫苗诱导抗肿瘤免疫应答，并用于消除MCSC以防止肿瘤再生长。
In previous study the streptavidin interleukin-2 (SA-IL-2)-modified MB49 vaccine was effective against bladder cancer in a mouse model. However, a small portion of tumors regrew because the vaccine could not eliminate MB49 bladder cancer stem cells (MCSCs). Accordingly, we developed a SA-IL-2-modified MCSCs vaccine and evaluated its antitumor effects. MCSCs were isolated and identified in cancer stem cells (CSCs) characters, with high expression of CSCs markers, higher resistance to chemotherapy, greater migration in vitro, and stronger tumorigenicity in vivo. The SA-IL-2 MCSCs vaccine was prepared and its bioactivity was evaluated. The protective, therapeutic, specific and memory immune response in animal experiments were designed to identify whether the vaccine elicited antitumor immunity and acted against metastatic bladder cancer. MCSCs had higher level of CD133 and CD44, less susceptibility to chemotherapy, more pronounced migration and greater tumorigenic ability. The successfully prepared SA-IL-2 MCSCs vaccine inhibited the tumor volume and prolonged mice survival in animal experiments. The expression of IgG, the population of dendritic cells, CD8+ and CD4+ T cells were highest in the experimental group than in the four control groups. The SA-IL-2 MCSCs vaccine induced an antitumor immune response and was used to eliminate MCSCs to prevent tumor regrowth.