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

Hongjun Li; Zejun Wang; Edikan A Ogunnaike; Qing Wu; Guojun Chen; Quanyin Hu; Tianyuan Ci; Zhaowei Chen; Jinqiang Wang; Di Wen; Hongwei Du; Jie Jiang; Jie Sun; Xingcai Zhang; Gianpietro Dotti; Zhen Gu

doi:10.1093/nsr/nwab172

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

Natl Sci Rev. 2021 Sep 21;9(3):nwab172. doi: 10.1093/nsr/nwab172. eCollection 2022 Mar.

Authors

Hongjun Li¹, Zejun Wang², Edikan A Ogunnaike³, Qing Wu¹, Guojun Chen², Quanyin Hu⁴, Tianyuan Ci², Zhaowei Chen¹, Jinqiang Wang¹, Di Wen², Hongwei Du⁵, Jie Jiang⁶, Jie Sun⁶, Xingcai Zhang⁷, Gianpietro Dotti⁵, Zhen Gu¹

Affiliations

¹ College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
² Department of Bioengineering, University of California, Los Angeles, CA 90095, USA.
³ Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
⁴ Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA.
⁵ Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
⁶ Department of Cell Biology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
⁷ John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.

Abstract

Chimeric antigen receptor T cell (CAR T) therapy was 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 implement 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 the 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.

Keywords: CAR T therapy; cell delivery; drug delivery; microneedle patch; solid tumor treatment.

Abstract

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