160 SORAFENIB ENHANCES THE ANTI-TUMOR EFFECT OF ANTI-CTLA-4 ANTIBODY TO KIDNEY CANCER

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You have accessJournal of UrologyKidney Cancer: Basic Research (I)1 Apr 2013160 SORAFENIB ENHANCES THE ANTI-TUMOR EFFECT OF ANTI-CTLA-4 ANTIBODY TO KIDNEY CANCER Motoshima Takanobu, komohara Yoshihiro, Kawano Yoshiaki, Wada Yoshihiro, and Eto Masatoshi Motoshima TakanobuMotoshima Takanobu Kumamoto, Japan More articles by this author , komohara Yoshihirokomohara Yoshihiro Kumamoto, Japan More articles by this author , Kawano YoshiakiKawano Yoshiaki Kumamoto, Japan More articles by this author , Wada YoshihiroWada Yoshihiro Kumamoto, Japan More articles by this author , and Eto MasatoshiEto Masatoshi Kumamoto, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1540AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Sorafenib is one of multikinase inhibitors widely used in patients with advanced kidney cancer. It exerts its anti-tumor effect not only by inhibiting signal pathways in cancer cells but also by constraining myeloid-derived suppressor cells (MDSC). Recently novel antibody against CTLA-4 that activates lymphocyte has been developed and is now under clinical trials. The aim of this study is to investigate whether low-dose sorafenib could augment the anti-tumor effect of anti-CTLA4 antibody (CTLA-4 Ab) in the murine kidney cancer model. METHODS RENCA cells were inoculated subcutaneously to BALB/c mice, and mice were randomly divided into 4 groups, including (1) low-dose sorafenib (10 mg/kg) plus CTLA-4 Ab, (2) low-dose sorafenib plus PBS, (3) vehicle plus CTLA-4 Ab, and (4) vehicle plus PBS. Sorafenib or vehicle control were administered orally once daily for 7 days to 21 days. CTLA-4 Ab was administered intraperitoneally at day 7, day 12 and day 17. The mice were sacrificed at day 21, then tumor infiltrating lymphocyte was analyzed by immunohistochemistry. RESULTS All three treatment groups ((1), (2) and (3)) showed a statistically significant decrease in tumor size compared with vehicle plus PBS group. In particular, combination of low-dose sorafenib and CTLA-4 Ab exhibited the most significant anti-tumor effect. Increase in infiltrating CD4- or CD8-positive lymphocyte was detected in CTLA-4 Ab alone group and low-dose sorafenib plus CTLA-4 Ab group. Especially, combination of low-dose sorafenib and CTLA-4 Ab demonstrated the most potent effect to trigger the infiltration of both CD4-positive lymphocyte and CD8-positive lymphocytes. These in vivo results indicate that sorafenib bolsters the immunostimulatory effect of CTLA-4 Ab even at the low dose. CONCLUSIONS Combination therapy of low-dose sorafenib and anti-CTLA-4 antibody can be a potential therapeutic option for advanced kidney cancer patients. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e66 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Motoshima Takanobu Kumamoto, Japan More articles by this author komohara Yoshihiro Kumamoto, Japan More articles by this author Kawano Yoshiaki Kumamoto, Japan More articles by this author Wada Yoshihiro Kumamoto, Japan More articles by this author Eto Masatoshi Kumamoto, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...