A deep insight into CRISPR/Cas9 application in CAR-T cell-based tumor immunotherapies

Stem Cell Research & Therapy

Heshu Sulaiman Rahman¹  Mahyuddin K. M. Nasution²  Somayeh Shamlou³  Walid Kamal Abdelbasset⁴  Surendar Aravindhan⁵  Siavash Shariatzadeh⁶  Zhanna R. Gardanova⁷  Farhad Motavalli Khiavi⁸  Wanich Suksatan⁹  Ehsan Razeghian^1,10  Faroogh Marofi^1,11  Dmitry O. Bokov^1,12  Pooria Nakhaei^1,13  Roza Motavalli^1,14  Mahboubeh Yazdanifar^1,15 

[1] College of Medicine, University of Sulaimani, Sulaymaniyah, Iraq;Department of Medical Laboratory Sciences, Komar University of Science and Technology, Sulaymaniyah, Iraq;DS & CI Research Group, Universitas Sumatera Utara, Medan, Indonesia;Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran;Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al Kharj, Saudi Arabia;Department of Physical Therapy, Kasr Al-Aini Hospital, Cairo University, Giza, Egypt;Department of Pharmacology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, India;Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran;Department of Psychotherapy, Pirogov Russian National Research Medical University, 1 Ostrovityanova St, 117997, Moscow, Russia;Department of Virology, Pasteur Institute of Iran, Tehran, Iran;Faculty of Nursing, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, 10210, Bangkok, Thailand;Human Genetics Division, Medical Biotechnology Department, National Institute of Genetics Engineering and Biotechnology (NIGEB), Tehran, Iran;Immunology Research Center (IRC), Tabriz University of Medical Sciences, Tabriz, Iran;Institute of Pharmacy, Sechenov First Moscow State Medical University, 8 Trubetskaya St., bldg. 2, 119991, Moscow, Russian Federation;Laboratory of Food Chemistry, Federal Research Center of Nutrition, Biotechnology and Food Safety, 2/14 Ustyinsky pr, 109240, Moscow, Russian Federation;School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA;

关键词: CRISPR-Cas9;    CAR-T cell;    Universal CAR-T cell;    Genome editing technologies;    Immune checkpoints;   

DOI  :  10.1186/s13287-021-02510-7

来源: Springer

【 摘 要 】

To date, two chimeric antigen receptors (CAR)-T cell products from autologous T cells have been approved by The United States Food and Drug Administration (FDA). The case-by-case autologous T cell generation setting is largely considered as a pivotal restraining cause for its large-scale clinical use because of the costly and prolonged manufacturing procedure. Further, activated CAR-T cells mainly express immune checkpoint molecules, including CTLA4, PD1, LAG3, abrogating CAR-T anti-tumor activity. In addition, CAR-T cell therapy potently results in some toxicity, such as cytokine releases syndrome (CRS). Therefore, the development of the universal allogeneic T cells with higher anti-tumor effects is of paramount importance. Thus, genome-editing technologies, in particular, clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 are currently being used to establish “off-the-shelf” CAR-T cells with robust resistance to immune cell-suppressive molecules. In fact, that simultaneous ablation of PD-1, T cell receptor alpha constant (TRAC or TCR), and also β-2 microglobulin (B2M) by CRISPR-Cas9 technique can support the manufacture of universal CAR-T cells with robust resistance to PD-L1. . Indeed, the ablation of β2M or TARC can severely hinder swift elimination of allogeneic T cells those express foreign HLA-I molecules, and thereby enables the generation of CAR-T cells from allogeneic healthy donors T cells with higher persistence in vivo. Herein, we will deliver a brief overview of the CAR-T cell application in the context of tumor immunotherapy. More importantly, we will discuss recent finding concerning the application of genome editing technologies for preparing universal CAR-T cells or cells that can effectively counter tumor escape, with a special focus on CRISPR-Cas9 technology.

【 授权许可】

CC BY