Optimization of Non-Ablative Focused Ultrasound Therapy for Tumor Immunity

 描述(申请人提供)：该项目的总体目标是开发一种安全的、非侵入性的、非消融性的聚焦超声疗法(NAFU)，可用于治疗原发癌和通过提高肿瘤的免疫原性来预防转移。NAFU治疗可作为当前治疗方法的一种辅助治疗，如化疗、免疫治疗、手术、放射治疗和HIFU。这项提案将确定NAFU在产生系统性抗肿瘤免疫中的作用，并确定诱导ER应激和增强肿瘤免疫调节标记物的特定方案，如热休克蛋白70、钙网蛋白、ATP和HMGB1。NAFU将与两种不同的新型免疫疗法相结合：基于树突状细胞的疫苗和基于李斯特菌的前列腺癌疫苗。初步数据表明，NAFU治疗增加了细胞表面的免疫调节，当与树突状细胞体外培养时，将导致增强的自体疫苗。此外，初步研究表明，对以李斯特菌为基础的减毒活疫苗进行NAFU治疗可以增强细菌的吞噬能力，从而产生更强大的免疫反应和控制肿瘤负担。这些项目将巩固非消融性聚焦超声作为一种有效的癌症治疗选择，它将诱导系统抗肿瘤免疫，治疗原发肿瘤，并减少转移。

 DESCRIPTION (provided by applicant): The overall goal of this project is to develop a safe, non-invasive non-ablative focused ultrasound therapy (NAFU) which can be used for the treatment of primary carcinoma and prevention of metastases by increasing tumor immunogenicity. NAFU treatment be used as an adjuvant therapy with current therapies, such as chemotherapy, immunotherapy, surgery, radiotherapy, and HIFU. This proposal will establish the role of NAFU in generating systemic anti-tumor immunity and define specific protocols for inducing ER stress and augmenting tumor immunomodulatory markers, such as heat shock protein 70, calreticulin, ATP and HMGB1. NAFU will be combined with two different novel immunotherapies: a dendritic cell-based vaccine and a Listeria-based prostate cancer vaccine. Preliminary data indicates that NAFU-treatment increases cell surface immunomodulation, which when cultured with dendritic cells ex vivo will result in an enhanced autologous vaccine. Additionally, preliminary studies demonstrate that NAFU-treatment of a live, attenuated Listeria-based vaccine for prostate cancer enhances phagocytosis of the bacteria, resulting in a more robust immune response and control of tumor burden. Together these projects will solidify non-ablative focused ultrasound as an effective cancer treatment option which will induce systemic anti-tumor immunity, treat primary tumors, and reduce metastases.