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(Peer-Reviewed) Scattered seeding of CAR T cells in solid tumors augments anticancer efficacy
Hongjun Li 李洪军 ¹ ² ³ ⁴ ⁵, Zejun Wang 王则君 ³ ⁴ ⁵, Edikan Archibong ⁶ ⁷, Qing Wu ¹, Guojun Chen 陈国军 ³ ⁴ ⁵, Quanyin Hu ⁷, Tianyuan Ci 慈天元 ³ ⁴ ⁵, Zhaowei Chen 陈兆委 ¹ ³ ⁴ ⁵, Jinqiang Wang 王金强 ¹ ³ ⁴ ⁵, Di Wen 温迪 ³ ⁴ ⁵, Hongwei Du 杜红伟 ⁶ ⁷, Jie Jiang ⁸, Jie Sun 孙洁 ⁸, Xingcai Zhang 张兴才 ⁹, Gianpietro Dotti ⁶ ⁷, Zhen Gu 顾臻 ¹ ² ³ ⁴ ⁵
¹ College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
中国 杭州 浙江大学药学院
² Liangzhu Laboratory, Zhejiang University Medical Center, Sir Run Run Shaw Hospital,
Hangzhou 310058, China
中国 杭州 邵逸夫医院 浙江大学医学中心良渚实验室
³ Department of Bioengineering, University of California, Los Angeles, CA 90095 USA
⁴ Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095 USA
⁵ California NanoSystems Institute, University of California, Los Angeles, CA 90095 USA
⁶ Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA
⁷ Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
⁸ Department of Cell Biology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
中国 杭州 浙江大学医学院 附属第一医院 骨髓移植中心
⁹ John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA
National Science Review , 2021-09-21
Abstract

Chimeric antigen receptor T cell (CAR T) therapy reached a milestone in the treatment of relapsed and refractory B-cell malignancies. However, beneficial effects of CAR T cells have not been obtained in solid tumors yet. Herein, we implemented a porous microneedle patch that accommodates CAR T cells and allows in situ penetration-mediated seeding of CAR T cells when implanted in the tumor bed or in post-surgical resection cavity.

CAR T cells loaded in the pores of the microneedle tips were readily escorted to the tumor in an evenly scattered manner without losing their activity. Such microneedle-mediated local delivery enhanced infiltration and immunostimulation of CAR T cells as compared to direct intratumoral injection. This tailorable patch offers a transformative platform for scattered seeding of living cells for treating a variety of tumors.
Scattered seeding of CAR T cells in solid tumors augments anticancer efficacy_1
Scattered seeding of CAR T cells in solid tumors augments anticancer efficacy_2
Scattered seeding of CAR T cells in solid tumors augments anticancer efficacy_3
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