Mp60-01 Hydrogel-Encapsulated Exosome Vaccine as a Novel Immunotherapeutic Approach and Its Role in Enhancing Immunotherapy for Prostate Cancer

You have accessJournal of UrologyProstate Cancer: Advanced (Including Drug Therapy) III (MP60)1 May 2024MP60-01 HYDROGEL-ENCAPSULATED EXOSOME VACCINE AS A NOVEL IMMUNOTHERAPEUTIC APPROACH AND ITS ROLE IN ENHANCING IMMUNOTHERAPY FOR PROSTATE CANCER Qi Chen, Zehong Peng, Yang Ge, Xinxing Du, Feihu Wang, Liang Dong, and Wei Xue Qi ChenQi Chen , Zehong PengZehong Peng , Yang GeYang Ge , Xinxing DuXinxing Du , Feihu WangFeihu Wang , Liang DongLiang Dong , and Wei XueWei Xue View All Author Informationhttps://doi.org/10.1097/01.JU.0001008804.84010.ec.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Due to the low immune cell infiltration and the suppressive tumor immune microenvironment (TIME), the efficacy of immunotherapy for prostate cancer is currently quite limited. This study aims to design a cancer vaccine using supramolecular peptide hydrogel encapsulated with ex vivo tumor tissue-derived exosomes (TEXs) and adjuvants to inhibit the growth and recurrence of prostate cancer, as well as improve the effect of immune checkpoint inhibitors. METHODS: Here, we design an amphiphilic self-assembling peptide, KKFE8, capable of forming hydrogels in situ after subcutaneous injection. TEXs are extracted through the lysis and ultracentrifugation of tumor tissue collected from prostate cancer patients. The positively charged self-assembler KKFE8 can adsorb negatively charged TEXs, CDA (a STING agonist), and GM-CSF through electrostatic interactions to create the Gel-Vaccine system. We characterize the controlled release of the vaccine components through the gel by in vitro and in vivo experiments. We then assess the therapeutic effects and related molecular mechanisms of gel vaccines in different mouse models of prostate cancer. RESULTS: Significant tumor regression was observed in mice vaccinated with the Gel-Vaccine across multiple mouse models of prostate cancer. This effect was even more pronounced in mice treated with the combination of aPD-1. We detected a higher number of DC aggregates at the site of gel vaccination, with an increased presence of mature and migratory DCs. Furthermore, we observed an elevated count of mature DCs, along with an increased presence of CD4+ and CD8+ T lymphocytes in the lymph nodes. Additionally, a greater number of CD8+ T cells with cytotoxic capabilities and fewer regulatory T cells infiltrates were detected within the tumor tissue. CONCLUSIONS: TEXs are enriched with tumor antigens, making them potential stimulators of anti-tumor immune responses. After subcutaneous inoculation, the exosome-gel scaffold can be triggered in situ to form an artificial secondary lymphoid organ, continuously recruiting antigen-presenting cells and achieving highly efficient antigen processing. This process can induce immune infiltration in the TIME. When combined with aPD-1, it triggers a potent and long-lasting tumor-specific immune response, effectively inhibiting prostate cancer growth and recurrence. This innovative approach suggests a new strategy for treating prostate cancer: customized gel vaccines from individual tumor-derived exosomes, offering personalized therapies. Source of Funding: N/A © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e999 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Qi Chen More articles by this author Zehong Peng More articles by this author Yang Ge More articles by this author Xinxing Du More articles by this author Feihu Wang More articles by this author Liang Dong More articles by this author Wei Xue More articles by this author Expand All Advertisement PDF downloadLoading ...