Injectable thermo-sensitive hydrogel enhances anti-tumor potency of engineered Lactococcus lactis by activating dendritic cells and effective memory T cells  

作　　者：Aoxing Chen Junmeng Zhu Rui Liu Yi Mei Lin Li Yue Fan Yaohua Ke Baorui Liu Qin Liu 

机构地区：[1]Department of Oncology,Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine,The Clinical Cancer Institute of Nanjing University,321 Zhongshan Road,Nanjing,210008,China [2]The Comprehensive Cancer Centre,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University,321 Zhongshan Road,Nanjing,210008,China [3]The Comprehensive Cancer Centre,China Pharmaceutical University Nanjing Drum Tower Hospital,321 Zhongshan Road,Nanjing,210008,China

出　　处：《Bioactive Materials》2024年第7期331-347,共17页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundation of China (82272811 and 81930080);the Fund for Distinguished Young Scholars of Jiangsu Province (BK20230001).

摘　　要：Engineered bacteria have shown great potential in cancer immunotherapy by dynamically releasing therapeutic payloads and inducing sustained antitumor immune response with the crosstalk of immune cells.In previous studies,FOLactis was designed,which could secret an encoded fusion protein of Fms-related tyrosine kinase 3 ligand and co-stimulator OX40 ligand,leading to remarkable tumor suppression and exerting an abscopal effect by intratumoral injection.However,it is difficult for intratumoral administration of FOLactis in solid tumors with firm texture or high internal pressure.For patients without lesions such as abdominal metastatic tumors and orthotopic gastric tumors,intratumoral injection is not feasible and peritumoral maybe a better choice.Herein,an engineered bacteria delivery system is constructed based on in situ temperature-sensitive poloxamer 407 hydrogels.Peritumoral injection of FOLactis/P407 results in a 5-fold increase in the proportion of activated DC cells and a more than 2-fold increase in the proportion of effective memory T cells(TEM),playing the role of artificial lymph island.Besides,administration of FOLactis/P407 significantly inhibits the growth of abdominal metastatic tumors and orthotopic gastric tumors,resulting in an extended survival time.Therefore,these findings demonstrate the delivery approach of engineered bacteria based on in situ hydrogel will promote the efficacy and universality of therapeutics.

关 键 词：Cancer immunotherapy Engineered bacteria Thermos-sensitive hydrogel Localized drug delivery Artificial lymph node 

分 类 号：TQ427.26[化学工程]