Cyclophosphamide loaded thermo-responsive hydrogel system synergize with a hydrogel cancer vaccine to amplify cancer immunotherapy in a prime-boost manner  

作　　者：Fan Yang Kun Shi Ying Hao Yanpeng Jia Qingya Liu Yu Chen Meng Pan Liping Yuan Yongyang Yu Zhiyong Qian 

机构地区：[1]State Key Laboratory of Biotherapy and Cancer Center,Collaborative Innovation Center for Biotherapy,West China Hospital,Sichuan University,Chengdu,610041,PR China [2]Department of Gastrointestinal Surgery,West China Hospital,Sichuan University,Chengdu,610041,PR China

出　　处：《Bioactive Materials》2021年第10期3036-3048,共13页生物活性材料（英文）

基　　金：This work was financially supported by the National Natural Science Foundation of China(31930067,31525009,31800797 and 31771096);the National Key Research and Development Program of China(2017YFC1103502);China Postdoctoral Science Foundation(2018M631094 and 2019M653410);1⋅3⋅5project for disciplines of excellence,West China Hospital,Sichuan University(ZYGD18002).

摘　　要：Although neoantigen-based cancer vaccines show great potential in cancer immunotherapy due to their ability to induce effective and long-lasting anti-tumor immunity,their development is hindered by the limitations of neoantigens identification,low immunogenicity,and weak immune response.Cyclophosphamide(CTX)not only directly kills tumors but also causes immunogenic cell death,providing a promising source of antigens for cancer vaccines.Herein,a combined immunotherapy strategy based on temperature-sensitive PLEL hydrogel is designed.First,CTX-loaded hydrogel is injected intratumorally into CT26 bearing mice to prime anti-tumor immunity,and then 3 days later,PLEL hydrogels loaded with CpG and tumor lysates are subcutaneously injected into both groins to further promote anti-tumor immune responses.The results confirm that this combined strategy reduces the toxicity of CTX,and produces the cytotoxic T lymphocyte response to effectively inhibit tumor growth,prolong survival,and significantly improve the tumor cure rate.Moreover,a long-lasting immune memory response is observed in the mice.About 90%of the cured mice survive for at least 60 days after being re-inoculated with tumors,and the distant tumor growth is also well inhibited.Hence,this PLEL-based combination therapy may provide a promising reference for the clinical promotion of chemotherapy combined with cancer vaccines.

关 键 词：IMMUNOTHERAPY Thermo-responsive hydrogels Immunogenic cell death Cancer vaccine CYCLOPHOSPHAMIDE 

分 类 号：R73[医药卫生—肿瘤] R318[医药卫生—临床医学]