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Strengthening the CAR-T Cell Therapeutic Application using CRISPR/Cas9 Technology
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  • Muhammad Sadeqi Nezhad,
  • Mahboubeh Yazdanifar,
  • Meghdad Abdollahpour-Alitappeh,
  • Arash Sattari,
  • Alexander seifalian,
  • Nader Bagheri
Muhammad Sadeqi Nezhad
Islamic Azad University
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Mahboubeh Yazdanifar
Stanford University School of Medicine
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Meghdad Abdollahpour-Alitappeh
Larestan University of Medical Sciences
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Arash Sattari
Islamic Azad University
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Alexander seifalian
University College London
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Nader Bagheri
Shahrekord University of Medical Science
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Abstract

Adoptive cell immunotherapy with chimeric antigen receptor (CAR) T cell has brought a revolutionary means of treatment for aggressive diseases such as hematologic malignancies and solid tumors. Over the last decade, FDA approved three types of CAR-T cells against CD19 hematologic malignancies, including Tisagenlecleucel (Kymriah), Axicabtagene ciloleucel (Yescarta), and Brexucabtagene autoleucel (Tecartus). Despite outstanding results gained from different clinical trials, CAR-T cell therapy is not free from side effects and toxicities, and needs careful investigations and improvements. Gene-editing technology, clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR-associated protein 9 (Cas9) system has emerged as a promising tool to address some of the CAR-T therapy hurdles. Using CRISPR/Cas9 technology, CAR expression as well as other cellular pathways can be modified in various ways to enhance CAR-T cell’s anti-tumor function and persistence in immunosuppressive tumor microenvironment. CRISPR/Cas9 technology can also be utilized to reduce CAR-T cells toxicity and side effects. Hereby, we discuss the practical challenges and hurdles related to the accuracy, efficiency, efficacy, safety and delivery of CRISPR/Cas9 technology to the genetically engineered-T cells. Combining of these two state-of-the-art technologies, CRISPR/Cas9 and CAR-T cells, the field of oncology has an extraordinary opportunity to enter a new era of immunotherapy, which offers novel therapeutic options for different types of tumors.

Peer review status:IN REVISION

05 May 2021Submitted to Biotechnology and Bioengineering
06 May 2021Assigned to Editor
06 May 2021Submission Checks Completed
09 May 2021Reviewer(s) Assigned
16 Jun 2021Review(s) Completed, Editorial Evaluation Pending
16 Jun 2021Editorial Decision: Revise Minor