Converting bacteria into autologous tumor vaccine via surface biomineralization of calcium carbonate for enhanced immunotherapy

作     者：Lina Guo Jinsong Ding Wenhu Zhou 

作者机构：Xiangya School of Pharmaceutical SciencesCentral South UniversityChangsha 410013China Key Laboratory of Biological Nanotechnology of National Health CommissionXiangya HospitalChangsha 410008China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2023年第13卷第12期

页      面：5074-5090页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(No.82073799) the Natural Science Foundation of Hunan Province in China(2021JJ20084) the Science and Technology Innovation Program of Hunan Province in China(2021RC3020). 

主　　题：Bacteria-mediated cancer therapy Tumor microenvironment Calcium carbonate Mineralization Metalloimmunology Autologous tumor vaccine Immunotherapy Tumor metastasis 

摘      要：Autologous cancer vaccine that stimulates tumor-specific immune responses for personalized immunotherapy holds great potential for tumor therapy.However,its efficacy is still suboptimal due to the immunosuppressive tumor microenvironment(ITM).Here,we report a new type of bacteria-based autologous cancer vaccine by employing calcium carbonate(CaCO_(3))biomineralized Salmonella(Sal)as an in-situ cancer vaccine producer and systematical ITM regulator.CaCO_(3) can be facilely coated on the Sal surface with calcium ionophore A23187 co-loading,and such biomineralization did not affect the bioactivities of the bacteria.Upon intratumoral accumulation,the CaCO_(3) shell was decomposed at an acidic microenvironment to atenuate tumor acidity,accompanied by the release of Sal and Ca^(2+)/A23187.Specifically,Sal served as a cancer vaccine producer by inducing cancer cells immunogenic cell death(ICD)and promoting the gap junction formation between tumor cells and dendritic cells(DCs)to promote antigen presentation.Ca^(2+),on the other hand,was intermalized into various types of immune cells with the aid of A23187 and synergized with Sal to systematically regulate the immune system,including DCs maturation,macrophages polarization,and T cells activation.As a result,such bio-vaccine achieved remarkable effcacy against both primary and metastatic tumors by eliciting potent anti-tumor immunity with full biocompatibility.This work demonstrated the potential of bioengineered bacteria as bio-active vaccines for enhanced tumor immunotherapy.