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ANTI-TUMOR EFFECTS OF AN IMIDAZOQUINOLINE IN RENAL CELL CARCINOMA

ANTI-TUMOR EFFECTS OF AN IMIDAZOQUINOLINE IN RENAL CELL CARCINOMA. Michael Schwartz, MD 3/14/2007. What are imidazoquinolines?. Family of immune response modifiers of which imiquimod is the most commonly used.

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ANTI-TUMOR EFFECTS OF AN IMIDAZOQUINOLINE IN RENAL CELL CARCINOMA

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  1. ANTI-TUMOR EFFECTSOF AN IMIDAZOQUINOLINE IN RENAL CELL CARCINOMA Michael Schwartz, MD 3/14/2007

  2. What are imidazoquinolines? • Family of immune response modifiers of which imiquimod is the most commonly used. • Act on Toll-like receptors which can increase cellular production of TNF, IFN-, and a variety of other cytokines. • Shown to improve antigen presentation by dendritic cells • Imiquimod is FDA approved for topical treatment of genital condyloma and basal cell carcinoma.

  3. Project Background • Renal cell carcinoma (RCC) responds to immunomodulators (IL-2, IFN-) • Imiquimod has been used as an immune response modifier in basal cell carcinoma • We hypothesized that imidazoquinolines may have direct in vitro and in vivo biological activity against renal cell carcinoma.

  4. Study Design • 4 renal cell carcinoma cell lines used • 1 mouse (RENCA) • 3 human (CAKI-1, CAKI-2, A-498) Experimental drug: 3M-011 • Closely related to Imiquimod (3M Pharmaceuticals) • Potential for use as an oral agent

  5. Do renal cell carcinoma cell lines express Toll-like receptor 7?

  6. Can 3M-011 affect cell viability? • Evaluated by cell counts • Cells cultured in with media supplemented with 3M-011at 100 g/ml • Cells harvested and counted at 24, 48, and 72 hour time points

  7. Potential correlation between cell viability and level of TLR-7 expression

  8. Figure 2

  9. In vivo affects of 3M-011 on a murine metastatic RCC model

  10. In vivo results • 30% of mice in 3M-011 group showed no pathologic evidence of tumor

  11. 3M-011 PLACEBO

  12. Summary and Conclusions • TLR-7 is expressed in both murine and human renal cancer cell lines. • Imidazoquinolines have direct biological effects on renal cell carcinoma cell lines by decreasing cell viability and inducing apoptosis. • Our results suggest a potential correlation between the TLR-7 expression level and the effect of 3M-011 on cell viability. • Initial results in an immune competent mouse model of metastatic renal cell carcinoma suggest anti-tumor effects in vivo.

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