A placebo-controlled efficacy study of the intravesical immunomodulators TMX-101 and TMX-202 in an orthotopic bladder cancer rat model

Purpose TMX-101 and TMX-202 are formulations of toll-like receptor 7 (TLR-7) agonists, under investigation for the treatment of urothelial carcinoma. Our goal was to evaluate the efficacy of intravesical instillations of TMX-101 or TMX-202 in an orthotopic bladder cancer rat model. Methods Four grou...

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Bibliographic Details
Published in:World journal of urology 2018-11, Vol.36 (11), p.1719-1725
Main Authors: Falke, Johannes, Hulsbergen-van de Kaa, Christina A., Maj, Roberto, Oosterwijk, Egbert, Witjes, J. Alfred
Format: Article
Language:English
Subjects:
Antitumor activity
Antiviral drugs
Bladder cancer
Immunomodulation
Invasiveness
Medicine
Medicine & Public Health
Nephrology
Oncology
Rodents
Sodium chloride
Statistical analysis
Toll-like receptors
Topic Paper
Toxicity
Tumor cells
Urology
Urothelial carcinoma
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Summary:Purpose TMX-101 and TMX-202 are formulations of toll-like receptor 7 (TLR-7) agonists, under investigation for the treatment of urothelial carcinoma. Our goal was to evaluate the efficacy of intravesical instillations of TMX-101 or TMX-202 in an orthotopic bladder cancer rat model. Methods Four groups of 14 rats received an instillation with isogenic AY-27 tumor cells on day 0, starting tumor development. On day 2 and 5, the rats were treated with an intravesical instillation of TMX-101 0.1%, TMX-202 0.38%, vehicle solution or NaCl. On day 12 the rats were sacrificed and the bladders were evaluated histopathologically. Results No signs of toxicity were seen. The number of tumor-positive rats was 11 of 14 (79%) in the vehicle control group and in the NaCl control group, versus 9 of 14 (64%) in the TMX-101-treated group, and 8 of 14 (57%) in the TMX-20-treated group. The difference between tumor-bearing rats in the treated and control groups was not significant ( p  = 0.12). Bladder weight was significantly lower for TMX-202-treated rats compared to vehicle ( p  = 0.005). Conclusions TMX-101 and TMX-202 are TLR-7 agonists with antitumor activity. Treatment with TMX-101 and TMX-202 resulted in less tumor-bearing rats compared to vehicle or saline control groups, although not statistically significant. In this aggressive bladder cancer model, a lower number of tumor-positive rats after treatment with TLR-7 agonists indicates activity for the treatment of non-muscle invasive bladder cancer.
ISSN:0724-4983
1433-8726
DOI:10.1007/s00345-018-2334-3