Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
J Urol. 2012 Mar;187(3):1071-9. doi: 10.1016/j.juro.2011.10.126. Epub 2012 Jan 21.
Immunotherapy is considered effective for muscle invasive bladder cancer mini metastasis. We developed what is to our knowledge a novel technology by which streptavidin tagged mouse GM-CSF was displayed on the surface of biotinylated bladder cancer cells to induce antitumor immunity.
Mouse subcutaneous and lung metastasis bladder cancer models were established. Mice were injected subcutaneously with 1 × 10(6) mouse GM-CSF surface modified MB49 bladder cancer cells and monitored for tumor growth and survival. Immunohistochemical and flow cytometric assay were done to assess the proportion of T lymphocytes. The T-lymphocyte cytotoxicity assay was performed to assess MB49 specific cytotoxicity. On day 60 after MB49 implantation the vaccine cured mice were injected subcutaneously with MB49 or RM-1 cells in the left or right hind leg, respectively. They were monitored for survival and T-lymphocyte cytotoxicity.
Mouse GM-CSF surface modified vaccine significantly inhibited tumor growth in the subcutaneous model and extended survival in the lung model. More CD4 and CD8 T cells appeared at tumor sites and in peripheral blood in the vaccine treated group than in other control groups. Splenocytes from the vaccine treated group showed the most potent cytotoxicity on MB49 cells. Cured mice in the vaccine treated group resisted the second injection of MB49 bladder cancer cells but not the RM-1 prostate cancer cell challenge.
Mouse GM-CSF surface modified MB49 bladder cancer cell vaccine induced specific antitumor immunity and was efficient for metastatic bladder cancer.
免疫疗法被认为对肌肉浸润性膀胱癌微转移有效。我们开发了一种新技术，即将生物素化的膀胱癌细胞表面展示链霉亲和素标记的小鼠 GM-CSF，以诱导抗肿瘤免疫。
建立了小鼠皮下和肺转移膀胱癌模型。将 1×10(6)个小鼠 GM-CSF 表面修饰的 MB49 膀胱癌细胞皮下注射给小鼠，并监测肿瘤生长和存活情况。通过免疫组织化学和流式细胞术检测 T 淋巴细胞的比例。进行 T 淋巴细胞细胞毒性试验以评估 MB49 特异性细胞毒性。在 MB49 植入后 60 天，用 MB49 或 RM-1 细胞分别在左后肢或右后肢对疫苗治愈的小鼠进行皮下注射，并监测其存活情况和 T 淋巴细胞细胞毒性。
小鼠 GM-CSF 表面修饰的疫苗显著抑制了皮下模型中的肿瘤生长，并延长了肺模型中的存活时间。在疫苗治疗组中，肿瘤部位和外周血中出现了更多的 CD4 和 CD8 T 细胞。来自疫苗治疗组的脾细胞对 MB49 细胞显示出最强的细胞毒性。疫苗治疗组的治愈小鼠抵抗了第二次 MB49 膀胱癌细胞的注射，但不抵抗 RM-1 前列腺癌细胞的挑战。
小鼠 GM-CSF 表面修饰的 MB49 膀胱癌细胞疫苗诱导了特异性抗肿瘤免疫，对转移性膀胱癌有效。
