Arch Iran Med. 2019;22(1):7-10.
PMID: 30821155
Scopus id: 85062433022
  Abstract View: 369
  PDF Download: 343

Original Article

Generation of CD19-Targeted Chimeric Antigen Receptor T Cells

Jafar Kiani 1,2, Mahmood Naderi 3 * , Monireh Torabi-Rahvar 2, Azam Ranjbar 2, Hamid-Reza Aghayan 4, Ehsan Janzamin 5, Naser Ahmadbeigi 3 *

1 Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
2 SABZ Biomedicals Science-Based Company, Tehran, Iran
3 Cell-Based Therapies Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
4 Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
5 Flowcyte Science-Based Company, Tehran, Iran
6 Flowcyte Science-Based Company, Tehran, Iran

Abstract

Background: Current advancements in the field of chimeric antigen receptor (CAR) therapy, particularly U.S. FDA approval of Kymriah and Yescarta, heralds a new era of cancer treatment. This rapid progress in technology has urged more countries and institutions to keep pace with the fast-growing and developing technology of producing CAR T cell-based therapies in the race to develop new cancer-targeting drugs. Hence, for stepping in line with global advances and to pave the way for subsequent preclinical and clinical studies, we have established a development protocol for a cancer-targeting CAR T cell; we have chosen CD19 CAR T cell as a well-defined model to set-up T cell expansion, activation, and viral transduction as the prerequisites for diverse CAR T cell therapies.

Methods: T cells from peripheral blood mononuclear cells (PBMCs) were activated and expanded. CD19 CAR lentiviral particles were produced in the Lenti-X™ 293T Cell Line using PolyFect Transfection Reagent.

Results: Activation protocol resulted in (65 ± 4%; P = 0.046) increase in the rate of activated T cells 24 hours after the initiation of the procedure. The expansion methodology resulted in a high purity of the T cell population (96 ± 3%) in the pool of PBMCs within 14 days of the procedure. Finally, 35 ± 6% of T cells were transduced with CD19 lentivirus with MOI of 3.

Conclusion: Collectively, the results of this study prove that we have successfully overcome the first hurdle on the road to reach CAR T cell technology which is the prerequisite for developing preclinical and clinical phases of CAR therapy in settings with basic resources

Cite this article as: Kiani J, Naderi M, Torabi-Rahvar M, Ranjbar A, Aghayan HR, Janzamin E, et al. Generation of CD19-targeted chimeric antigen receptor T cells. Arch Iran Med. 2019;22(1):7–10.
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Submitted: 23 Sep 2018
Accepted: 01 Dec 2018
First published online: 01 Jan 2019
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