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.
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.
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).
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.
World journal of urology. 2018 May 16 [Epub ahead of print]
Johannes Falke, Christina A Hulsbergen-van de Kaa, Roberto Maj, Egbert Oosterwijk, J Alfred Witjes
Department of Urology, Radboud University Nijmegen Medical Center, Geert Grooteplein Zuid 10 (610), P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands., Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands., Telormedix SA, Bioggio, Switzerland., Department of Urology, Radboud University Nijmegen Medical Center, Geert Grooteplein Zuid 10 (610), P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. .