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2008 Annual Meeting Abstracts
Immunotherapy Of Superficial Bladder Carcinoma With Intravesical Chitosan/il-12 Is Superior To Bcg Treatment In A Mouse Bladder Cancer Model
Compton J Benjamin, Jr.*, David A Zaharoff*, Benjamin Hoffman*, H. Brooks Hooper*, Kiranpreet K. Khurana*, Kenneth W Hance*, Connie J Rogers*, Jeffrey Schlom*, John W Greiner*, Peter A Pinto
National Institutes of Health, Bethesda, MD
Introduction: The failure to complete intravesical BCG treatment for bladder cancer is likely due to its side effects. IL-12, an inflammatory cytokine produced in high levels in bladders of BCG treated patients, complexed to a viscous chitosan solution may offer similar effectiveness with decreased adverse effects.
Methods: Mice bearing luciferase transfected non-immunogenic orthotopic bladder tumors (MB49.Luc) were treated intravesically with PBS, IL-12 alone, chitosan alone, or chitosan/IL-12 after tumor instillation and monitored for luciferase activity. Chitosan/IL-12 was also compared to BCG in mice bearing orthotopic MB49.Luc bladder tumors.
Results: At day 40, three of 5 mice treated with IL-12 alone were tumor-free, while 100% of mice treated with chitosan/IL-12 were tumor free. All control mice died within 35 days. Serum assays of mice treated with intravesical chitosan/IL12 also demonstrated higher serum levels of IL-12 and IFN-γ 24 hours after administration, compared to IL-12 alone, implying that chitosan facilitated greater local delivery of IL-12. Furthermore, all eight of the tumor-free mice rejected tumor rechallenge. Histological analysis of bladders from chitosan/IL-12 treated mice revealed no gross pathology.The median survival of mice treated with BCG was no different than that of control mice. However, chitosan/IL-12 treatment completely eradicated tumors in 55% of mice suggesting that chitosan/IL-12 is superior to BCG in the treatment of orthotopic MB49 tumors. Moreover, none of the chitosan/IL-12 mice showed any overt symptoms of toxicity when treated with chitosan/IL-12.
Conclusions: This suggests that chitosan/IL-12 may be a safe, translatable and durable immunotherapy for the treatment of superficial bladder cancer.
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