The therapeutic potential of recombinant BCG expressing the antigen S1PT in the intravesical treatment of bladder cancer
The therapeutic potential of recombinant BCG expressing the antigen S1PT in the intravesical treatment of bladder cancer
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DOI：
10.1016/j.urolonc.2008.12.017
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发表时间：
2010-09-01
影响因子：
2.7
通讯作者：
Srougi, Miguel
中科院分区：
文献类型：
--
作者：
Andrade, Priscila M.;Chade, Daher C.;Srougi, Miguel
目的：卡介苗（BCG）仍然是治疗浅表性膀胱癌最有效的免疫疗法。我们已经开发了一种rBCG-S1 PT菌株，它比BCG诱导更强的细胞免疫应答。本临床前研究的目的是测试潜在的rBCG-S1 PT作为一种免疫抑制剂intravesical膀胱cancer therapy.Materials和方法：一个肿瘤诱导C57 BL/6小鼠化学烧灼后的膀胱和接种的肿瘤细胞系MB 49。接下来，通过膀胱内滴注BCG、rBCG-S1 PT或PBS每周一次治疗小鼠，持续4周。35天后，取出膀胱并称重，通过定量真实的时间PCR测量单个小鼠膀胱中的Th 1（IL-2、IL-12、INOS、INF-γ、TNF-α）和Th 2（IL-5、IL-6、IL-10、TGF-β）细胞因子mRNA应答，并评估MB 49细胞在与来自处理小鼠的脾细胞共培养18小时中的存活力。结果：BCG和rBCG-S1 PT免疫治疗均能使膀胱重量减轻，rBCG-S1 PT组与对照组相比生存时间延长。BCG治疗组中TNF-α升高，rBCG-S1 PT组中TNF-α和IL-10 mRNA升高。MB 49细胞与rBCG-S1 PT治疗小鼠脾细胞共培养的存活率低于BCG和对照组。结论：rBCG-S1 PT治疗改善了预后，延长了生存时间。这些结果表明rBCG可以作为野生型BCG的有用替代品。(C)2010年爱思唯尔公司All rights reserved.
Purpose: Bacillus Calmette-Guerin (BCG) continues to be employed as the most effective immunotherapy against superficial bladder cancer. We have developed an rBCG-S1PT strain that induces a stronger cellular immune response than BCG. This preclinical study was designed to test the potential of rBCG-S1PT as an immunotherapeutic agent for intravesical bladder cancer therapy.Materials and methods: A tumor was induced in C57BL/6 mice after chemical cauterization of the bladder and inoculation of the tumor cell line MB49. Next, mice were treated by intravesical instillation with BCG, rBCG-S1PT, or PBS once a week for 4 weeks. After 35 days, the bladders were removed and weighed, Th1 (IL-2, IL-12, INOS, INF-gamma, TNF-alpha), and Th2 (IL-5, IL-6, IL-10, TGF-beta) cytokine mRNA responses in individual mice bladders were measured by quantitative real time PCR, and the viability of MB49 cells in 18-hour coculture with splenocytes from treated mice was assessed. In an equivalent experiment, animals were observed for 60 days to quantify their survival.Results: Both BCG and rBCG-S1PT immunotherapy resulted in bladder weight reduction, and rBCG-S1PT increased survival time compared with the control group. There were increases in TNF-alpha in the BCG treated group, as well as increases in TNF-alpha and IL-10 mRNA in the rBCG-S1PT group. The viability of MB49 cells cocultured with splenocytes from rBCG-S1PT-treated mice was lower than in both the BCG and control groups.Conclusions: rBCG-S1PT therapy improved outcomes and lengthened survival times. These results indicate that rBCG could serve as a useful substitute for wild-type BCG. (C) 2010 Elsevier Inc. All rights reserved.