Abstract
Abstract Introduction: EphA2 and HSP90 play important roles in tumor growth, survival and metastasis. An effective therapeutic approach would promote decreased expression of EphA2 on tumor cells, while increasing presentation of EphA2-derived peptides on tumor MHC class I complexes, thereby enhancing the recognition of tumors by anti-EphA2 CD8+ T effector cells. Aim: We are assessing the safety and effectiveness of the HSP90 inhibitor 17-DMAG in enhancing anti-tumor immunotherapy with EphA2-specific T cells in murine tumor models. Methods: We tested the effect of 17-DMAG on tumor cell expression of EphA2 and the MHC I antigen-processing machinery in vitro. Efficacy of 17-DMAG in an MCA205 sarcoma model was also evaluated in vivo. Results: 17-DMAG facilitated a dose-dependent reduction in EphA2 expression, but had no adverse effects on the antigen-processing machinery of the tumors. Similar effects were seen in an MCA205 sarcoma model in vivo, where reduction in EphA2 levels in tumors corresponded with increased recognition by EphA2-specific CD8+ T cells in vitro. 17-DMAG treatment also facilitated increased infiltration of CD4 and CD8 T cells in the tumor, compared to untreated cohorts. Conclusion: 17-DMAG treatment promotes immunologically-preferred alterations tumor cells in vitro as well as In vivo. Our preliminary in vivo studies suggest that decreased EphA2 levels in tumors is accompanied by increased presentation of EphA2 peptides in tumor MHC class I complexes. Further in vivo studies are warranted to assess the net anti-tumor impact of combinational immunotherapies integrating 17-DMAG. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1805. doi:10.1158/1538-7445.AM2011-1805
Published Version
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