Epsilon-caprolactone-modified polyethylenimine as a genetic vehicle for stem cell-based bispecific antibody and exosome synergistic therapy  

作　　者：Yan Tan Jiali Cai Zhiyong Wang 

机构地区：[1]Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging,School of Biomedical Engineering,Health Science Center,Shenzhen University,Shenzhen 518060,China [2]Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education,School of Materials Science and Engineering,Center for Functional Biomaterials,Sun Yat-Sen University,Guangzhou 510275,China

出　　处：《Regenerative Biomaterials》2023年第1期97-106,共10页再生生物材料（英文版）

基　　金：was supported by the Natural Science Foundation of the Guangdong Province(2021A1515011799);the National Natural Science Foundation of China(NSFC)(Grant nos 81471778 and 81602499).

摘　　要：Bispecific antibodies(BsAb)have gained significant momentum in clinical application.However,the rapid enzymolysis and metabolism of protein drugs usually induce short circulation in vivo,and developing an efficient protein delivery system still is a bottleneck.Mesenchymal stem cells(MSCs)have become an attractive therapeutic carrier for cancers.Genetic modification enables MSCs to express and secrete specific proteins,which is essential for therapeutic efficacy.However,efficient gene transfer into MSCs is still a challenge.In this study,we applied epsilon-caprolactone-modified polyethylenimine(PEI-CL)as an efficacy carrier for plasmid transfection into MSC that served as in situ‘cell factory’for anti-CD3/CD20 BsAb preparation.Herein,the PEI-CL encapsulates the minicircle plasmid and mediates cell transfection efficiently.Thus,the anti-CD3/CD20 BsAb is secreted from MSC and recruited T cell,resulting in highly sensitive cytotoxicity in the human B-cell lymphoma.Furthermore,these stem cells produce exosomes bearing MiR-15a/MiR-16,which could negatively regulate cancer’s oncogenes BCL-2 for adjuvant therapy.Meanwhile,high immunologic factors like tumor necrosis factor-αand interferon-γare generated and enhance immunotherapy efficacy.The engineered MSCs are demonstrated as an efficient route for BsAb production,and these bioactive components contribute to synergistic therapy,which would be an innovative treatment.

关 键 词：POLYETHYLENIMINE stem cell bispecific antibody EXOSOME 

分 类 号：R318[医药卫生—生物医学工程]