Loskog A, Ninalga C, Hedlund T, Alimohammadi M, Malmström P-U, Tötterman T H
Clinical Immunology Division, Rudbeck Laboratory, Uppsala University, Sweden.
Lab Anim. 2005 Oct;39(4):384-93. doi: 10.1258/002367705774286475.
Bladder cancer is regarded as a promising candidate for innovative therapies in the field of immune and gene therapy. In this paper, we present the subcutaneous, metastatic and a novel orthotopic model of murine MB49 bladder cancer in C57BL/6 mice. We further show the potential of using adenoviral vectors together with different transduction enhancers to augment in vivo gene delivery. Finally, we present candidate genes for tumour detection, therapy or targeting. The MB49 tumour grew rapidly in mice. The subcutaneous model allowed for tumour detection within a week and the possibility to monitor growth rate on a day-by-day basis. Injection of MB49 cells intravenously into the tail vein gave rise to lung metastases within 16 days, while instillation of tumour cells into pretreated bladders led to a survival time of 20-40 days. Adenoviral vectors can be used as a vehicle for gene transfer to the bladder. By far, the most potent transduction enhancer was Clorpactin, also known as oxychlorosene. Last, we show that MB49 cells express tumour-associated antigens like bladder cancer-4, prostate stem cell antigen and six-transmembrane epithelial antigen of the prostate. Given the possibility for efficient genetic modification of the bladder and the presence of known tumour antigens, the MB49 models can be used in innovative ways to explore immunogene therapy.
膀胱癌被视为免疫和基因治疗领域创新疗法的一个有前景的候选对象。在本文中，我们展示了C57BL/6小鼠中MB49小鼠膀胱癌的皮下、转移和一种新型原位模型。我们进一步展示了使用腺病毒载体与不同转导增强剂一起增强体内基因递送的潜力。最后，我们提出了用于肿瘤检测、治疗或靶向的候选基因。MB49肿瘤在小鼠体内生长迅速。皮下模型在一周内即可检测到肿瘤，并且有可能逐日监测生长速度。将MB49细胞经尾静脉静脉注射在16天内导致肺转移, 而将肿瘤细胞灌注到预处理的膀胱中导致生存时间为20 - 40天。腺病毒载体可作为基因转移至膀胱的载体。到目前为止，最有效的转导增强剂是氯帕丁，也称为羟氯柳苯胺。最后，我们表明MB49细胞表达肿瘤相关抗原，如膀胱癌-4、前列腺干细胞抗原和前列腺六跨膜上皮抗原。鉴于对膀胱进行有效基因改造的可能性以及已知肿瘤抗原的存在，MB49模型可用于以创新方式探索免疫基因治疗。
