| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Cancer Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 [Y. A. S., E. C. B.], 3M Pharmaceuticals, 3M Company, St. Paul, Minnesota 55144 [C. E. W., M. J. R.], and the University of Wisconsin Clinical Cancer Center, Madison, Wisconsin 53792 [J. F. H., G. T. B.]
The low-molecular-weight imidazoquinolinamine derivative, 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine (imiquimod, previously described as R-837), induced 
-interferon (IFN-) in mice. IFN induction was identified at oral doses as low as 3 mg/kg. The 10% lethal dose for daily treatment with imiquimod was 200 mg/kg. Oral treatment with 30 mg/kg imiquimod once every three days significantly inhibited MC-26 colon carcinoma. Delay of treatment from day 1 to day 5, when tumors were easily palpable, did not reduce benefits. Ten daily treatments were slightly more effective than five. However, delivery of the same total dose of imiquimod either once every day for 20 days, once every 4 days, once every 7 days, or once every 10 days inhibited tumor growth to the same level. The antitumor effects of imiquimod were significantly abrogated by an antiserum to murine IFN-, suggesting that the antitumor effect was to a substantial extent mediated by IFN induction. Imiquimod also significantly reduced the number of lung colonies in mice inoculated i.v. with MC-26 tumor cells. Combination of treatment with imiquimod and cyclophosphamide was significantly (P < 0.01) better than treatment with either drug alone. Combination treatment with cyclophosphamide led to cures in some of the mice inoculated either s.c. or i.v. with MC-26 cells. Treatment with imiquimod also inhibited the growth of RIF-1 sarcoma and Lewis lung carcinoma but was ineffective for P388 leukemia. Imiquimod is an oral IFN- inducer with antitumor effectiveness for transplantable murine tumors.
1 Supported in part by grants from 3M Pharmaceuticals, 3M Company, St. Paul, MN. E. C. B. is an American Cancer Society Professor of Clinical Oncology.
2 To whom requests for reprints should be addressed, at Cancer Center, Medical College of Wisconsin, 8901 Watertown Plank Road, Milwaukee, WI 53226.
Received 9/20/91. Accepted 4/24/92.
This article has been cited by other articles:
|
|
 |
|
  L. A. J. O'Neill, C. E. Bryant, and S. L. Doyle Therapeutic Targeting of Toll-Like Receptors for Infectious and Inflammatory Diseases and Cancer Pharmacol. Rev., June 1, 2009; 61(2): 177 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Broomfield, R. G. van der Most, A. C. Prosser, S. Mahendran, M. G. Tovey, M. J. Smyth, B. W. S. Robinson, and A. J. Currie Locally Administered TLR7 Agonists Drive Systemic Antitumor Immune Responses That Are Enhanced by Anti-CD40 Immunotherapy J. Immunol., May 1, 2009; 182(9): 5217 - 5224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Fahey, A. B. Raff, D. M. Da Silva, and W. M. Kast Reversal of Human Papillomavirus-Specific T Cell Immune Suppression through TLR Agonist Treatment of Langerhans Cells Exposed to Human Papillomavirus Type 16 J. Immunol., March 1, 2009; 182(5): 2919 - 2928. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. S. Zagon, R. N. Donahue, M. Rogosnitzky, and P. J. Mclaughlin Imiquimod Upregulates the Opioid Growth Factor Receptor to Inhibit Cell Proliferation Independent of Immune Function Experimental Biology and Medicine, August 1, 2008; 233(8): 968 - 979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. J. M. Smits, P. Ponsaerts, Z. N. Berneman, and V. F. I. Van Tendeloo The Use of TLR7 and TLR8 Ligands for the Enhancement of Cancer Immunotherapy Oncologist, August 1, 2008; 13(8): 859 - 875. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Dummer, A. Hauschild, J. C. Becker, J.-J. Grob, D. Schadendorf, V. Tebbs, J. Skalsky, K. C. Kaehler, S. Moosbauer, R. Clark, et al. An Exploratory Study of Systemic Administration of the Toll-like Receptor-7 Agonist 852A in Patients with Refractory Metastatic Melanoma Clin. Cancer Res., February 1, 2008; 14(3): 856 - 864. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Stary, C. Bangert, M. Tauber, R. Strohal, T. Kopp, and G. Stingl Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells J. Exp. Med., June 11, 2007; 204(6): 1441 - 1451. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Kelishadi, G. A. Wirth, and G. R. D. Evans Recalcitrant verrucous lesion: verrucous hyperplasia or epithelioma cuniculatum (verrucous carcinoma). J Am Podiatr Med Assoc, March 1, 2006; 96(2): 148 - 153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Chaperot, A. Blum, O. Manches, G. Lui, J. Angel, J.-P. Molens, and J. Plumas Virus or TLR Agonists Induce TRAIL-Mediated Cytotoxic Activity of Plasmacytoid Dendritic Cells J. Immunol., January 1, 2006; 176(1): 248 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Craft, K. W. Bruhn, B. D. Nguyen, R. Prins, J. W. Lin, L. M. Liau, and J. F. Miller The TLR7 Agonist Imiquimod Enhances the Anti-Melanoma Effects of a Recombinant Listeria monocytogenes Vaccine J. Immunol., August 1, 2005; 175(3): 1983 - 1990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Palamara, S. Meindl, M. Holcmann, P. Luhrs, G. Stingl, and M. Sibilia Identification and Characterization of pDC-Like Cells in Normal Mouse Skin and Melanomas Treated with Imiquimod J. Immunol., September 1, 2004; 173(5): 3051 - 3061. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nair, C. McLaughlin, A. Weizer, Z. Su, D. Boczkowski, J. Dannull, J. Vieweg, and E. Gilboa Injection of Immature Dendritic Cells into Adjuvant-Treated Skin Obviates the Need for Ex Vivo Maturation J. Immunol., December 1, 2003; 171(11): 6275 - 6282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schon, A. B. Bong, C. Drewniok, J. Herz, C. C. Geilen, J. Reifenberger, B. Benninghoff, H. B. Slade, H. Gollnick, and M. P. Schon Tumor-Selective Induction of Apoptosis and the Small-Molecule Immune Response Modifier Imiquimod J Natl Cancer Inst, August 6, 2003; 95(15): 1138 - 1149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Doxsee, T. R. Riter, M. J. Reiter, S. J. Gibson, J. P. Vasilakos, and R. M. Kedl The Immune Response Modifier and Toll-Like Receptor 7 Agonist S-27609 Selectively Induces IL-12 and TNF-{alpha} Production in CD11c+CD11b+CD8- Dendritic Cells J. Immunol., August 1, 2003; 171(3): 1156 - 1163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fogel, J. A. Long, P. J. Thompson, and J. W. Upham Dendritic cell maturation and IL-12 synthesis induced by the synthetic immune-response modifier S-28463 J. Leukoc. Biol., November 1, 2002; 72(5): 932 - 938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Shumack, J. Robinson, S. Kossard, L. Golitz, H. Greenway, A. Schroeter, K. Andres, M. Amies, and M. Owens Efficacy of Topical 5% Imiquimod Cream for the Treatment of Nodular Basal Cell Carcinoma: Comparison of Dosing Regimens Arch Dermatol, September 1, 2002; 138(9): 1165 - 1171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Moisan, W. Wojciechowski, C. Guilbault, C. Lachance, S. Di Marco, E. Skamene, G. Matlashewski, and D. Radzioch Clearance of Infection with Mycobacterium bovis BCG in Mice Is Enhanced by Treatment with S28463 (R-848), and Its Efficiency Depends on Expression of Wild-Type Nramp1 (Resistance Allele) Antimicrob. Agents Chemother., November 1, 2001; 45(11): 3059 - 3064. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Bishop, Y. Hsing, B. S. Hostager, S. V. Jalukar, L. M. Ramirez, and M. A. Tomai Molecular Mechanisms of B Lymphocyte Activation by the Immune Response Modifier R-848 J. Immunol., November 15, 2000; 165(10): 5552 - 5557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Lipper, K. A. Arndt, and J. S. Dover Recent Therapeutic Advances in Dermatology JAMA, January 12, 2000; 283(2): 175 - 177. [Full Text] [PDF]
|
|
|
|
|
|
L. Edwards, A. Ferenczy, L. Eron, D. Baker, M. L. Owens, T. L. Fox, A. J. Hougham, K. A. Schmitt, and and the HPV Study Group Self-administered Topical 5% Imiquimod Cream for External Anogenital Warts Arch Dermatol, January 1, 1998; 134(1): 25 - 30. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
