{"title":"植入式合成免疫水凝胶用于肿瘤源性免疫抑制和全身抗肿瘤免疫的时空调节","authors":"Chanyoung Song, Il Woo Shin, Long Ren, Y. Lim","doi":"10.1158/2326-6074.CRICIMTEATIAACR18-B133","DOIUrl":null,"url":null,"abstract":"The development of biomaterial-based immune niches that can shape tumor-induced immunosuppressive factors will play an important role to improve current cancer immunotherapy. Herein, we developed an engineered 3-dimensional porous scaffold for creating synergistic action between myeloid-derived suppressor cell (MDSC)-depleting drugs, which can revert an immunosuppressive tumor microenvironment to one supporting antitumor immunity, and cancer vaccines (whole tumor lysate-based antigens and nano-adjuvants carrying Toll-like receptor 3 agonists), which can induce tumor antigen-specific T-cell responses. The local implantation of the scaffold (called immuneCare-DISC, iCD) as a post-surgical treatment in large established 4T1 breast tumors induced systemic antitumor immunity and prevented relapse and metastasis, resulting in survival of 100%. These therapeutic results were obtained from the depletion of MDSCs by control releasing of gemcitabine and the recruitment/activation of dendritic cells, increased infiltrating of T-cells and enhanced level of IFN-γ production by sustained releasing of cancer vaccine from the iCD. This synthetic immune niche iCD as a spatiotemporal modulation of tumor-induced immunosuppression and cancer vaccine-induced immune stimulation is proposed to generate favorable environment to prevent recurrence and metastasis following the surgical resection. Citation Format: Chanyoung Song, Il Woo Shin, Long Ren, Yong Taik Lim. Implantable synthetic immune hydrogel for spatiotemporal modulation of tumor-derived immunosuppression and systemic antitumor immunity [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B133.","PeriodicalId":19329,"journal":{"name":"Novel Vaccine Platforms and Combinations","volume":"4 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Abstract B133: Implantable synthetic immune hydrogel for spatiotemporal modulation of tumor-derived immunosuppression and systemic antitumor immunity\",\"authors\":\"Chanyoung Song, Il Woo Shin, Long Ren, Y. 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These therapeutic results were obtained from the depletion of MDSCs by control releasing of gemcitabine and the recruitment/activation of dendritic cells, increased infiltrating of T-cells and enhanced level of IFN-γ production by sustained releasing of cancer vaccine from the iCD. This synthetic immune niche iCD as a spatiotemporal modulation of tumor-induced immunosuppression and cancer vaccine-induced immune stimulation is proposed to generate favorable environment to prevent recurrence and metastasis following the surgical resection. Citation Format: Chanyoung Song, Il Woo Shin, Long Ren, Yong Taik Lim. Implantable synthetic immune hydrogel for spatiotemporal modulation of tumor-derived immunosuppression and systemic antitumor immunity [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. 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引用次数: 0
摘要
基于生物材料的免疫龛的开发可以塑造肿瘤诱导的免疫抑制因子,将对改善当前的癌症免疫治疗发挥重要作用。在此,我们开发了一种工程化的三维多孔支架,用于在骨髓源性抑制细胞(MDSC)消耗药物和癌症疫苗(基于全肿瘤裂解物的抗原和携带toll样受体3激动剂的纳米佐剂)之间产生协同作用,这些药物可以将免疫抑制性肿瘤微环境恢复为支持抗肿瘤免疫的微环境)之间产生协同作用,后者可以诱导肿瘤抗原特异性t细胞反应。局部植入支架(称为immuneCare-DISC, iCD)作为4T1大乳腺肿瘤的术后治疗,可诱导全身抗肿瘤免疫,防止复发和转移,生存率为100%。这些治疗结果是通过控制吉西他滨的释放和树突状细胞的募集/激活,增加t细胞的浸润和通过从iCD持续释放癌症疫苗提高IFN-γ产生水平来消耗MDSCs获得的。这种合成免疫位iCD作为肿瘤诱导的免疫抑制和癌症疫苗诱导的免疫刺激的时空调节,为预防手术切除后的复发和转移创造有利的环境。引文格式:chanyyoung Song, Il Woo Shin, Long Ren, Yong Taik Lim。植入式合成免疫水凝胶时空调节肿瘤源性免疫抑制和全身抗肿瘤免疫[摘要]。第四届CRI-CIMT-EATI-AACR国际癌症免疫治疗会议:将科学转化为生存;2018年9月30日至10月3日;纽约,纽约。费城(PA): AACR;癌症免疫学杂志,2019;7(2增刊):摘要nr B133。
Abstract B133: Implantable synthetic immune hydrogel for spatiotemporal modulation of tumor-derived immunosuppression and systemic antitumor immunity
The development of biomaterial-based immune niches that can shape tumor-induced immunosuppressive factors will play an important role to improve current cancer immunotherapy. Herein, we developed an engineered 3-dimensional porous scaffold for creating synergistic action between myeloid-derived suppressor cell (MDSC)-depleting drugs, which can revert an immunosuppressive tumor microenvironment to one supporting antitumor immunity, and cancer vaccines (whole tumor lysate-based antigens and nano-adjuvants carrying Toll-like receptor 3 agonists), which can induce tumor antigen-specific T-cell responses. The local implantation of the scaffold (called immuneCare-DISC, iCD) as a post-surgical treatment in large established 4T1 breast tumors induced systemic antitumor immunity and prevented relapse and metastasis, resulting in survival of 100%. These therapeutic results were obtained from the depletion of MDSCs by control releasing of gemcitabine and the recruitment/activation of dendritic cells, increased infiltrating of T-cells and enhanced level of IFN-γ production by sustained releasing of cancer vaccine from the iCD. This synthetic immune niche iCD as a spatiotemporal modulation of tumor-induced immunosuppression and cancer vaccine-induced immune stimulation is proposed to generate favorable environment to prevent recurrence and metastasis following the surgical resection. Citation Format: Chanyoung Song, Il Woo Shin, Long Ren, Yong Taik Lim. Implantable synthetic immune hydrogel for spatiotemporal modulation of tumor-derived immunosuppression and systemic antitumor immunity [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B133.