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Production of Car T-Cells by Gmp-Grade Lentiviral Vectors: Latest Advances and Future Prospects Publisher Pubmed



Poorebrahim M1 ; Sadeghi S2 ; Fakhr E3 ; Abazari MF4 ; Poortahmasebi V5, 6, 7 ; Kheirollahi A8 ; Askari H9 ; Rajabzadeh A10 ; Rastegarpanah M1 ; Line A11 ; Cidarregui A2, 12
Authors
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Authors Affiliations
  1. 1. Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
  3. 3. Department of Translational Immunology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
  4. 4. Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Liver and Gastrointestinal Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  6. 6. Infectious and Tropical Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  7. 7. Faculty of Medicine, Department of Bacteriology and Virology, Tabriz University of Medical Sciences, Tabriz, Iran
  8. 8. Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
  9. 9. Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  10. 10. Applied Cell Sciences and Tissue Engineering Department, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  11. 11. Latvian Biomedical Research and Study Centre, Riga, Latvia
  12. 12. Targeted Tumor Vaccines Group, Clinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center (DKFZ), Heidelberg, Germany

Source: Critical Reviews in Clinical Laboratory Sciences Published:2019


Abstract

Chimeric antigen receptor (CAR) T-cells represent a paradigm shift in cancer immunotherapy and a new milestone in the history of oncology. In 2017, the Food and Drug Administration approved two CD19-targeted CAR T-cell therapies (Kymriah™, Novartis, and Yescarta™, Kite Pharma/Gilead Sciences) that have remarkable efficacy in some B-cell malignancies. The CAR approach is currently being evaluated in multiple pivotal trials designed for the immunotherapy of hematological malignancies as well as solid tumors. To generate CAR T-cells ex vivo, lentiviral vectors (LVs) are particularly appealing due to their ability to stably integrate relatively large DNA inserts, and to efficiently transduce both dividing and nondividing cells. This review discusses the latest advances and challenges in the design and production of CAR T-cells, and the good manufacturing practices (GMP)-grade production process of LVs used as a gene transfer vehicle. New developments in the application of CAR T-cell therapy are also outlined with particular emphasis on next-generation allogeneic CAR T-cells. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.
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