PD25-09 TUMOR ASSOCIATED ANTIGEN VACCINE ENHANCES ANTI-TUMOR EFFECTS OF IMMUNE CHECKPOINT INHIBITORS AGAINST REFRACTORY CANCERS

Abstract

You have accessJournal of UrologyCME1 Apr 2023PD25-09 TUMOR ASSOCIATED ANTIGEN VACCINE ENHANCES ANTI-TUMOR EFFECTS OF IMMUNE CHECKPOINT INHIBITORS AGAINST REFRACTORY CANCERS Shohei Ueda, Miho Ushijima, Atsushi Irie, Yasuharu Nishimura, and Masatoshi Eto Shohei UedaShohei Ueda More articles by this author , Miho UshijimaMiho Ushijima More articles by this author , Atsushi IrieAtsushi Irie More articles by this author , Yasuharu NishimuraYasuharu Nishimura More articles by this author , and Masatoshi EtoMasatoshi Eto More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003303.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Progressive and chemoresistant bladder cancer is problematic because of the poor prognosis. Immune checkpoint blockade (ICB) has exhibited drastic anti-tumor efficacy in some patients, but the response rates were limited. Therefore, to improve efficacy of immunotherapy for refractory cancer, we have tried to develop a combination immunotherapy of tumor antigen vaccine and ICB in tumor-bearing mouse models. METHODS: We identified genes highly expressed in tumors but not in normal tissues by comparing RNA-seq data of mouse bladder cancer MB49, cisplatin-resistant MB49-CR, and lymphoma RMA cell lines, all of which are refractory to ICB, with datasets of 26 normal mouse tissues. Subsequently tumor-associated antigens-derived peptides predicted to have high binding affinities to MHC-I and -II molecules were identified by prediction algorithms. We also selected immunogenic and cancer-specific mutated Neo-antigenic peptides. MB49, MB49-CR, or RMA bearing mice were treated with these peptides and ICB. Finally, we investigated tumor infiltrating immune cells by flow cytometry, T cell receptor (TCR) repertoire analysis and RNA-seq of inoculated tumors. RESULTS: In 50-80% of mice pre-immunized with identified peptides, growths of MB49 and RMA inoculated s.c. were prevented and these immunized mice rejected re-transplanted tumors. Furthermore, combination therapy of these peptide vaccines and ICB synergistically inhibited tumor-growth of MB49-CR, MB49 and RMA indicating that the combination immunotherapy enhances therapeutic efficacy to treat refractory cancers. We also observed combination therapy with MHC-I antigen vaccination and ICB synergistically increased limited CD8+ TCR-alpha and beta genes in tumors, suggesting increased antigen-specific tumor-infiltrating CD8+ T cells. Furthermore, combination therapy with MHC-I/II antigen vaccine and ICB synergistically induced drastic changes of various types of tumor-infiltrating immune cells such as CD8+ T cells, CD4+ type 1 helper T cells, regulatory CD4+ T cells and natural killer cells. CONCLUSIONS: These results suggest that the combination immunotherapy described above shapes tumor-infiltrating immune cells and enhances therapeutic efficacy to treat refractory cancer. Source of Funding: This work was supported by KAKENHI. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e732 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shohei Ueda More articles by this author Miho Ushijima More articles by this author Atsushi Irie More articles by this author Yasuharu Nishimura More articles by this author Masatoshi Eto More articles by this author Expand All Advertisement PDF downloadLoading ...