Обзорная статья

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

Hyatt Balke‐WantStanford Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, USAVimal KeerthiStanford Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, USAAmaia Cadiñanos-GaraiUSC/CHLA Cell Therapy Program, University of Southern California, and Children's Hospital Los Angeles, Los Angeles, USAChristabel E. FowlerStanford Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, USANikolaos GkitsasStanford Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, USAAnnie Kathleen BrownStanford Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, USARamya TunuguntlaStanford Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, USAMohamed Abou‐El‐EneinDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USAS. FeldmanStanford Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, USA

2023en

ABI

Аннотация

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.

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Идентификаторы

DOI: 10.1016/j.iotech.2023.100375

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar