239 RADIATION SENSITIZATION BY A CYTOTOXIC ANTI-β2-MICROGLOBULIN ANTIBODY FOR THE TREATMENT OF PROSTATE CANCER IN EXPERIMENTAL MODELS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research II1 Apr 2010239 RADIATION SENSITIZATION BY A CYTOTOXIC ANTI-β2-MICROGLOBULIN ANTIBODY FOR THE TREATMENT OF PROSTATE CANCER IN EXPERIMENTAL MODELS Yasuhiro Matsuoka, Sajni Josson, Murali Gururajan, Xiaojian Yang, and Leland Chung Yasuhiro MatsuokaYasuhiro Matsuoka More articles by this author , Sajni JossonSajni Josson More articles by this author , Murali GururajanMurali Gururajan More articles by this author , Xiaojian YangXiaojian Yang More articles by this author , and Leland ChungLeland Chung More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.297AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES β2-Microglobulin (β2M), a co-receptor for MHC-class 1 family proteins, was identified by our laboratory as a novel growth factor, a pleiotropic signaling molecule, and a prognostic factor for human prostate cancer. β2M was also shown to be able to expand mesenchymal stem cells. We developed a cytotoxic anti-β2M antibody (β2MAb) strategy to treat hormone refractory human prostate cancer (HRPC) both in culture and in mice. The objectives of this study are: 1) to determine if ionizing radiation can be used to synergize β2MAb activity to treat HRPC in ARCaPM and C4-2 human prostate cancer xenografts; and 2) to determine the effects of β2MAb on host immunity prior to future clinical translation in an immune-competent transgenic model of adenocarcinoma of the mouse prostate (TRAMP). METHODS The effectiveness of this antibody was evaluated in two models. Using the spontaneous TRAMP mouse model (age 15-24 weeks), we assessed the effects of β2MAb on tumor volumes by near infra-red fluorescence imaging, and host immunity by the measurement of CD4+ and CD8+ T cells and B cells in control C57BL6 and IgG treated and β2MAb-treated TRAMP mice. Using a nude mouse model, we assessed the effects of β2MAb on growth and serum PSA in human HRPC xenografts, ARCaPM and C4-2, respectively. RESULTS β2MAb inhibited the growth of TRAMP tumor cells in vitro and their ability to grow in syngeneic TRAMP mice. Control TRAMP mice had 60-100% tumor take whereas the β2MAb-treated group had 20% tumor take. Long term administration of β2MAb did not affect the numbers of CD4+ T cells, CD8+ T cells and B cells in the immune-competent mice. ARCaPM tumor xenografts were allowed to develop in the flanks of the mice. Intratumor administration of β2MAb plus irradiation treatment of 15 Gy completely blocked tumor growth. The growth of C4-2 tumor xenografts in mouse tibia, as assessed by serum PSA, was inhibited by β2MAb and radiation. Both osteolytic and osteoblastic lesions in mouse bone were prevented by 16% after the treatment of mice with β2MAb. CONCLUSIONS β2MAb can be used as an adjuvant cytotoxic antibody synergizing with ionizing radiation to enhance human prostate cancer cell-kill in nude mice and syngeneic mouse tumors grown in TRAMP animals, without compromising host immunity. Los Angeles, CA© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e93 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yasuhiro Matsuoka More articles by this author Sajni Josson More articles by this author Murali Gururajan More articles by this author Xiaojian Yang More articles by this author Leland Chung More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...