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Imiquimod: an Immune-Response Modifier for Transitional Cell Carcinoma of the Bladder

This study explores the potential of Imiquimod, a synthetic immunomodulator, as a treatment for transitional cell carcinoma of the bladder. In vitro and in vivo experiments show its direct effects on bladder cancer cells and preliminary evidence of anti-tumor effects.

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Imiquimod: an Immune-Response Modifier for Transitional Cell Carcinoma of the Bladder

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  1. IMIQUIMOD, AN IMMUNE-RESPONSE MODIFIER, IN THE TREATMENT OF TRANSITIONAL CELL CARCINOMA OF THE BLADDER Douglas Scherr, M.D. Department of Urology New York Presbyterian Hospital-Weill Cornell Medical Center

  2. Introduction • Imiquimod is a potent synthetic immunomodulator • Currently used as a first-line treatment for genital condyloma (Aldara, 3M) • Effective against several skin cancers including melanoma and basal cell carcinoma

  3. Introduction • Induces both innate and acquired immune responses • Toll-like receptor 7 (TLR-7) agonist • Stimulates dendritic cells to mature and secrete pro-inflammatory cytokines • Mechanism strikingly similar to bacillus Calmette-Guerin (BCG)

  4. Introduction • Hypothesis: • Imiquimod may have therapeutic potential against transitional cell carcinoma of the bladder • Objectives: • To determine if Imiquimod has direct effects on bladder cancer cells in vitro • To determine if Imiquimod has anti-tumor effects in vivo in an intact immune system

  5. In vitro Methods Cell Viability (MTT Assay) Imiquimod 24 hrs Apoptosis (TUNEL Assay) Bladder Cancer Cell Lines (J82, T24, TCC-SUP) Cytokine Production (ELISA)

  6. Cell Viability Figure 1. Cell Proliferation Assays

  7. Apoptosis Control (PBS) Group Imiquimod Group

  8. Apoptosis Control (PBS) Group Imiquimod Group

  9. Apoptosis 17.1% 0.8%

  10. 930 1340 425 480 Cytokine Production

  11. In vivo Methods • Orthotopic, syngeneic, immune competent mouse model (Bochner et al J. Urology, 2003) • Murine bladder tumor (MBT-2) cells instilled intravesically into C3H mice • Treatment regimen: • Day 0: Tumor cells instilled • Day 1: Treatment with Imiquimod or PBS • Day 8: Retreated • Day 15: Mice sacrificed

  12. Control (PBS) Imiquimod

  13. Conclusions • Imiquimod is a potent immune-response modifier • Has direct biological effects on bladder cancer cell lines • Preliminary data suggests anti-tumor effects in vivo • Imiquimod may be a potential immunotherapy for bladder cancer

  14. Acknowledgements PI: Douglas Scherr, MD Contributors: Hideki Kawamoto, MD Xuecke You, MD Mathew Albert, PhD

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