Presented October 25th - 28th, 2007 at the 2007 Urological Research Society (URS) Meeting - Napa, California

Objective: Sunitinib (Sutent®) is a tyrosine kinase inhibitor that targets the vascular endothelial growth factor receptor and platelet-derived growth factor receptor. Sutent® has recently been registered as first-line treatment for patients with mRCC. However, complete responses have been rare and most patient progress eventually. Thus, Sutent® represents the best, but still suboptimal treatment for mRCC and combination therapy might be beneficial. Chimeric mAb cG250 identifies carbonic anhydrase IX, abundantly over-expressed in RCC. Tumor accumulation of cG250 is the highest of any antibody in a solid tumor. Combination of Sutent® with mAb cG250 might lead to improved tumor responses and survival in patients with mRCC. The aim of this study was to explore the effect of Sutent® on mAb cG250 biodistribution.

Methods: Nude mice bearing human RCC xenografts were treated with Sutent® or solvent for 7 or 14 days. At day 7, mice were injected i.v. with ¹²⁵I-cG250. Animals were sacrificed at predetermined days and cG250 biodistribution determined. Tumors were analyzed by immunohistochemistry for the presence of endothelial cells, activated endothelial cells, laminin, smooth muscle actin and uptake of mAb cG250.

Results and Conclusion: While on Sutent® treatment tumor uptake of cG250 decreased dramatically, tumorgrowth was slightly inhibited and vascular density decreased considerably as judged by various markers. When treatment was stopped at day 7, neovascularization recovered immediately, mainly at the tumor periphery. Since Sutent® treatment leads to drastically decreased antibody uptake; combination treatment strategies with such agents may have a small window of opportunity and should be carefully designed.

Authors: Mulders PFA, Oosterwijk-Wakka JC, Kats G, Leenders W, Oosterwijk E

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