Abstract
PurposeTMX-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.MethodsFour 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.ResultsNo 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).ConclusionsTMX-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.
Highlights
At any point in time, 2.7 million people have a history of urothelial bladder cancer worldwide [1]
Intravesical instillation of bacillus Calmette–Guerin (BCG) induces a complex immune response leading to a Th-1 cell-mediated immune response responsible for cytotoxic T cell activity against urothelial carcinoma (UC) [4]
The goal of the toll-like receptor 7 (TLR-7) agonists TMX101 and TMX-202 is a local immune response leading to antitumor activity compared to BCG, but circumventing the use of live attenuated mycobacteria, and preventing side effects
Summary
At any point in time, 2.7 million people have a history of urothelial bladder cancer worldwide [1]. Of the newly diagnosed cases, around 70% is non-muscle invasive bladder cancer (NMIBC) [2]. BCG was the first successful immunotherapy for cancer and has been used for over 40 years to reduce the risk of bladder cancer recurrence as well as the risk of progression to muscle invasive disease. Intravesical instillation of BCG induces a complex immune response leading to a Th-1 cell-mediated immune response responsible for cytotoxic T cell activity against urothelial carcinoma (UC) [4]. This cellular response depends on the Toll like receptor (TLR) signaling system [5].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
