학술논문
Engineering Efficient CAR-T Cells via Electroactive Nanoinjection.
Document Type
Academic Journal
Author
Shokouhi AR; Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.; Melbourne Centre for Nanofabrication, Victorian Node of the Australian National Fabrication Facility, 151 Wellington Road, Clayton, VIC, 3168, Australia.; Chen Y; Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.; Melbourne Centre for Nanofabrication, Victorian Node of the Australian National Fabrication Facility, 151 Wellington Road, Clayton, VIC, 3168, Australia.; Yoh HZ; Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.; Melbourne Centre for Nanofabrication, Victorian Node of the Australian National Fabrication Facility, 151 Wellington Road, Clayton, VIC, 3168, Australia.; Brenker J; Dynamic Micro Devices (DMD) Lab, Department of Mechanical & Aerospace Engineering, Monash University, 17 College Walk, Clayton, VIC, 3168, Australia.; Alan T; Dynamic Micro Devices (DMD) Lab, Department of Mechanical & Aerospace Engineering, Monash University, 17 College Walk, Clayton, VIC, 3168, Australia.; Murayama T; Institute of Semiconductor and Electronics Technologies ULVAC Inc., 1220-1 Suyama, Susono, Shizuoka, 410-1231, Japan.; Suu K; Institute of Semiconductor and Electronics Technologies ULVAC Inc., 1220-1 Suyama, Susono, Shizuoka, 410-1231, Japan.; Morikawa Y; Institute of Semiconductor and Electronics Technologies ULVAC Inc., 1220-1 Suyama, Susono, Shizuoka, 410-1231, Japan.; Voelcker NH; Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.; Melbourne Centre for Nanofabrication, Victorian Node of the Australian National Fabrication Facility, 151 Wellington Road, Clayton, VIC, 3168, Australia.; Department of Materials Science and Engineering, Monash University, 22 Alliance Lane, Clayton, VIC, 3168, Australia.; Elnathan R; School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, VIC, 3216, Australia.; Institute for Frontier Materials, Deakin University, Geelong Waurn Ponds campus, Waurn Ponds, VIC, 3216, Australia.; The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong Waurn Ponds Campus, Melbourne, VIC, 3216, Australia.
Source
Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 9885358 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-4095 (Electronic) Linking ISSN: 09359648 NLM ISO Abbreviation: Adv Mater Subsets: MEDLINE
Subject
Language
English
Abstract
Chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising cell-based immunotherapy approach for treating blood disorders and cancers, but genetically engineering CAR-T cells is challenging due to primary T cells' sensitivity to conventional gene delivery approaches. The current viral-based method can typically involve significant operating costs and biosafety hurdles, while bulk electroporation (BEP) can lead to poor cell viability and functionality. Here, a non-viral electroactive nanoinjection (ENI) platform is developed to efficiently negotiate the plasma membrane of primary human T cells via vertically configured electroactive nanotubes, enabling efficient delivery (68.7%) and expression (43.3%) of CAR genes in the T cells, with minimal cellular perturbation (>90% cell viability). Compared to conventional BEP, the ENI platform achieves an almost threefold higher CAR transfection efficiency, indicated by the significantly higher reporter GFP expression (43.3% compared to 16.3%). By co-culturing with target lymphoma Raji cells, the ENI-transfected CAR-T cells' ability to effectively suppress lymphoma cell growth (86.9% cytotoxicity) is proved. Taken together, the results demonstrate the platform's remarkable capacity to generate functional and effective anti-lymphoma CAR-T cells. Given the growing potential of cell-based immunotherapies, such a platform holds great promise for ex vivo cell engineering, especially in CAR-T cell therapy.
(© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)
(© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)