Tumor nanovaccines have potential applications in the prevention and treatment of malignant tumors.However,it remains a longstanding challenge in exploiting efficient nanocarriers for inducing potent specifically cell...Tumor nanovaccines have potential applications in the prevention and treatment of malignant tumors.However,it remains a longstanding challenge in exploiting efficient nanocarriers for inducing potent specifically cellular immune responses.Toward this objective,we herein explore an intensive tumor immunotherapeutic strategy by combining mannosylated nanovaccines and gene regulated PD-L1 blockade for immune stimulation and killing activity.Here,we fabricate a mannose modified PLL-RT(Man-PLL-RT)mediated nanovaccines with dendritic cells(DCs)targeting capacity.Man-PLL-RT is capable of co-encapsulating with antigen(ovalbumin,OVA)and adjuvant(unmethylated cytosine-phosphate-guanine,CpG)by electrostatic interaction.This positively charged Man-PLL-RT/OVA/CpG nanovaccines can facilitate the endocytosis,maturation and cross presentation in DCs.However,the nanovaccines arouse limited inhibition of tumor growth,which is mainly due to the immunosuppressed microenvironment of tumors.Combining tumor nanovaccines with gene regulated PD-L1 blockade leads to an obvious tumor remission in B16F10 melanoma bearing mice.The collaborative strategy provides essential insights to boost the benefits of tumor vaccines by regulating the checkpoint blockade with gene therapy.展开更多
基金This work was supported by the National Natural Science Foundation of China(51925305,51873208,51973217,51520105004 and 51803210)National Science and Technology Major Projects for Major New Drugs Innovation and Development(2018ZX09711003-012)and Jilin Province Science and Technology Development Program(20180414027GH and 20200201075JC).
文摘Tumor nanovaccines have potential applications in the prevention and treatment of malignant tumors.However,it remains a longstanding challenge in exploiting efficient nanocarriers for inducing potent specifically cellular immune responses.Toward this objective,we herein explore an intensive tumor immunotherapeutic strategy by combining mannosylated nanovaccines and gene regulated PD-L1 blockade for immune stimulation and killing activity.Here,we fabricate a mannose modified PLL-RT(Man-PLL-RT)mediated nanovaccines with dendritic cells(DCs)targeting capacity.Man-PLL-RT is capable of co-encapsulating with antigen(ovalbumin,OVA)and adjuvant(unmethylated cytosine-phosphate-guanine,CpG)by electrostatic interaction.This positively charged Man-PLL-RT/OVA/CpG nanovaccines can facilitate the endocytosis,maturation and cross presentation in DCs.However,the nanovaccines arouse limited inhibition of tumor growth,which is mainly due to the immunosuppressed microenvironment of tumors.Combining tumor nanovaccines with gene regulated PD-L1 blockade leads to an obvious tumor remission in B16F10 melanoma bearing mice.The collaborative strategy provides essential insights to boost the benefits of tumor vaccines by regulating the checkpoint blockade with gene therapy.
