An injectable signal-amplifying device elicits a specific immune response against malignant glioblastoma  

作　　者：Qiujun Qiu Sunhui Chen Huining He Jixiang Chen Xinyi Ding Dongdong Wang Jiangang Yang Pengcheng Guo Yang Li Jisu Kim Jianyong Sheng Chao Gao Bo Yin Shihao Zheng Jianxin Wang 

机构地区：[1]Department of Pharmaceutics,School of Pharmacy,Fudan University&Key Laboratory of Smart Drug Delivery,Ministry of Education,Shanghai 201203,China [2]Department of Pharmacy,Fujian Provincial Hospital&Provincial Clinical Medical College of Fujian Medical University,Fuzhou 350001,China [3]Institute of Materia Medica,Academy of Chinese and Western Integrative Medicine,Fudan University,Shanghai 201203,China [4]Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics,School of Pharmacy,Tianjin Medical University,Tianjin 300070,China [5]Department of Radiology,Huashan Hospital,Fudan University,Shanghai 200040,China [6]Institute of Tropical Medicine,Guangzhou University of Chinese Medicine,Guangzhou 510006,China [7]Department of Neurosurgery,Fujian Provincial Hospital&Provincial Clinical Medical College of Fujian Medical University,Fuzhou 350001,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第12期5091-5106,共16页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.81773911,81690263,and 81573616);the Development Project of Shanghai Peak Disciplines-Integrated Medicine(No.20180101).

摘　　要：Despite exciting achievements with some malignancies,immunotherapy for hypoimmunogenic cancers,especially glioblastoma(GBM),remains a formidable clinical challenge.Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response.Herein,we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the"danger"signal of GBM.We demonstrated the feasibility of this strategy in two scenarios of GBM.In the first scenario,we showed that this simultaneous amplification system,in conjunction with local chemotherapy,enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model;thus,ultimately making a cold GBM hot and suppressing postoperative relapse.Encouraged by excellent efficacy,we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM,a disease with limited clinical treatment options.In general,this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractorymalignancies.

关 键 词：Immunotherapy GLIOBLASTOMA Antigen-capturing nanoparticles Recombinant chemokines Immune signal-amplifying 

分 类 号：R73-36[医药卫生—肿瘤]