1. The paths toward non-viral CAR-T cell manufacturing: A comprehensive review of state-of-the-art methods.
- Author
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Metanat Y, Viktor P, Amajd A, Kaur I, Hamed AM, Abed Al-Abadi NK, Alwan NH, Chaitanya MVNL, Lakshmaiya N, Ghildiyal P, Khalaf OM, Ciongradi CI, and Sârbu I
- Subjects
- Humans, Animals, T-Lymphocytes immunology, Genetic Therapy methods, Neoplasms therapy, Immunotherapy, Adoptive methods, Receptors, Chimeric Antigen genetics, Receptors, Chimeric Antigen immunology, Genetic Vectors
- Abstract
Although CAR-T cell therapy has emerged as a game-changer in cancer immunotherapy several bottlenecks limit its widespread use as a front-line therapy. Current protocols for the production of CAR-T cells rely mainly on the use of lentiviral/retroviral vectors. Nevertheless, according to the safety concerns around the use of viral vectors, there are several regulatory hurdles to their clinical use. Large-scale production of viral vectors under "Current Good Manufacturing Practice" (cGMP) involves rigorous quality control assessments and regulatory requirements that impose exorbitant costs on suppliers and as a result, lead to a significant increase in the cost of treatment. Pursuing an efficient non-viral method for genetic modification of immune cells is a hot topic in cell-based gene therapy. This study aims to investigate the current state-of-the-art in non-viral methods of CAR-T cell manufacturing. In the first part of this study, after reviewing the advantages and disadvantages of the clinical use of viral vectors, different non-viral vectors and the path of their clinical translation are discussed. These vectors include transposons (sleeping beauty, piggyBac, Tol2, and Tc Buster), programmable nucleases (ZFNs, TALENs, and CRISPR/Cas9), mRNA, plasmids, minicircles, and nanoplasmids. Afterward, various methods for efficient delivery of non-viral vectors into the cells are reviewed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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