Scattered seeding of CAR T cells in solid tumors augments anticancer efficacy

Author:

Li Hongjun12345,Wang Zejun345,Archibong Edikan67,Wu Qing1,Chen Guojun345,Hu Quanyin7,Ci Tianyuan345,Chen Zhaowei1345,Wang Jinqiang1345,Wen Di345,Du Hongwei67ORCID,Jiang Jie8,Sun Jie8,Zhang Xingcai9ORCID,Dotti Gianpietro67,Gu Zhen12345

Affiliation:

1. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China

2. Liangzhu Laboratory, Zhejiang University Medical Center, Sir Run Run Shaw Hospital, Hangzhou 310058, China

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

9. John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA

Abstract

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.

Publisher

Oxford University Press (OUP)

Subject

Multidisciplinary

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