1 / 14

Douglas Scherr, M.D. Department of Urology

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. Introduction. Imiquimod is a potent synthetic immunomodulator

susane
Download Presentation

Douglas Scherr, M.D. Department of Urology

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related