Non-viral chimeric antigen receptor (CAR) T cells going viral

H. Balke-Want; V. Keerthi; A. Cadinanos-Garai; C. Fowler; N. Gkitsas; A.K. Brown; R. Tunuguntla; M. Abou-el-Enein; S.A. Feldman

Immuno-Oncology and Technology (Jun 2023)

Non-viral chimeric antigen receptor (CAR) T cells going viral

H. Balke-Want,
V. Keerthi,
A. Cadinanos-Garai,
C. Fowler,
N. Gkitsas,
A.K. Brown,
R. Tunuguntla,
M. Abou-el-Enein,
S.A. Feldman

Affiliations

H. Balke-Want: Stanford Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, USA
V. Keerthi: Stanford Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, USA
A. Cadinanos-Garai: USC/CHLA Cell Therapy Program, University of Southern California, and Children’s Hospital Los Angeles, Los Angeles, USA
C. Fowler: Stanford Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, USA
N. Gkitsas: Stanford Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, USA
A.K. Brown: Stanford Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, USA
R. Tunuguntla: Stanford Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, USA
M. Abou-el-Enein: USC/CHLA Cell Therapy Program, University of Southern California, and Children’s Hospital Los Angeles, Los Angeles, USA; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA
S.A. Feldman: Stanford Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, USA; Correspondence to: Dr. Steven A. Feldman, Site Head and Scientific Director Laboratory for Cell and Gene Medicine, Stanford GMP Facility, Stanford School of Medicine/Stanford HealthCare, 855 California Avenue, Unit C, Mail code: 5538 Office: G100A, Stanford, CA 94304. Tel: (202) 421-7519

Journal volume & issue: Vol. 18
p. 100375

Abstract

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Chimeric antigen receptor (CAR) T cell therapy has made significant strides in the treatment of B-cell malignancies, but its application in treating solid tumors still poses significant challenges. Particularly, the widespread use of viral vectors to deliver CAR transgenes into T cells comes with limitations, including high costs and regulatory restrictions, which hinder the translation of novel genetic engineering concepts into clinical applications. Non-viral methods, such as transposon/transposase and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas systems, offer promising alternatives for stable transgene insertion in CAR-T cells. These methods offer the potential to increase accessibility and efficiency in the development and delivery of CAR-T cell therapies. The main challenge in using non-viral methods, however, is their low knock-in efficiency, which leads to low transgene expression levels. In this review, we discuss recent developments in non-viral approaches for CAR-T cell production, the manufacturing requirements for clinical-grade production of non-viral CAR-T cells, and the adjustments needed in quality control for proper characterization of genomic features and evaluation of potential genotoxicity.

Published in Immuno-Oncology and Technology

ISSN: 2590-0188 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/immuno-oncology-and-technology

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