首页|Lymph node-biomimetic scaffold boosts CAR-T therapy against solid tumor

Lymph node-biomimetic scaffold boosts CAR-T therapy against solid tumor

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The limited infiltration and persistence of chimeric antigen receptor(CAR)-T cells is primarily responsible for their treatment deficits in solid tumors.Here,we present a three-dimensional scaffold,inspired by the physiological process of T-cell proliferation in lymph nodes.This scaffold gathers the function of loading,delivery,activation and expansion for CAR-T cells to enhance their therapeutic effects on solid tumors.This porous device is made from poly(lactic-co-glycolic acid)by a microfluidic technique with the modification of T-cell stimulatory signals,including anti-CD3,anti-CD28 antibodies,as well as cytokines.This scaffold fosters a 50-fold CAR-T cell expansion in vitro and a 15-fold cell expansion in vivo.Particularly,it maintains long-lasting expansion of CAR-T cells for up to 30 days in a cervical tumor model and significantly inhibits the tumor growth.This biomimetic delivery strategy provides a versatile platform of cell delivery and activation for CAR-T cells in treating solid tumors.

drug deliverycell therapybioinspired biomaterialscancer immunotherapy

Ziyan Liao、Jie Jiang、Wei Wu、Jiaqi Shi、Yanfang Wang、Yuejun Yao、Tao Sheng、Feng Liu、Wei Liu、Peng Zhao、Feifei Lv、Jie Sun、Hongjun Li、Zhen Gu

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National Key Laboratory of Advanced Drug Delivery and Release Systems,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China

Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China

Liangzhu Laboratory,Zhejiang University,Hangzhou 311121,China

Bone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology,Zhejiang University School of Medicine,Hangzhou 310058,China

Oepartment of Medical Oncology,The First Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310003,China

Department of Laboratory Medicine,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China

Department of Hepatobiliary and Pancreatic Surgery,The Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310009,China

Jinhua Instit

Jinhua Institute of Zhejiang University,Jinhua 321299,China

MOE Key Laboratory of Macromolecular Synthesis and Functionalization of Ministry of Education,De

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国家自然科学基金国家自然科学基金国家重点研发计划Startup Package of Zhejiang University and China Postdoctoral Science Foundation

52233013521731422021YFA09099002022M712718

2024

10.1093/nsr/nwae018

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ISSN：
年,卷(期)：2024.11(4)
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