Optimization of the MB49 mouse bladder cancer model for adenoviral gene therapy.
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.
Loskog
A
A
Clinical Immunology Division, Rudbeck Laboratory, Uppsala University, Sweden. angelica.loskog@klinimm.uu.se
Ninalga
C
C
Hedlund
T
T
Alimohammadi
M
M
Malmström
P-U
PU
Tötterman
T H
TH
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D001557:Benzenesulfonates / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006182:H-Y Antigen / Q000096:biosynthesis / Q000235:genetics; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D014161:Transduction, Genetic / Q000379:methods; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
D000951:Antigens, Neoplasm; D001557:Benzenesulfonates; D014408:Biomarkers, Tumor; D006182:H-Y Antigen; D012334:RNA, Neoplasm; C018120:oxychlorosene