Strengthening the CAR‐T cell therapeutic application using CRISPR/Cas9 technology

Nezhad, Muhammad Sadeqi; Yazdanifar, Mahboubeh; Abdollahpour‐Alitappeh, Meghdad; Sattari, Arash; Seifalian, Alexander M.; Bagheri, Nader

doi:10.1002/bit.27882

Cited by 17 publications

(11 citation statements)

References 110 publications

(114 reference statements)

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“… 48 Currently, only five CAR-T products have been approved, for hematologic malignancies, by the United States Food and Drug Administration (FDA) which are (i) Abecma (idecabtagene vicleucel) for patients with relapsed or refractory (R/R) myeloma, (ii) Breyanzi (lisocabtagene maraleucel) for R/R large B-cell lymphoma patients, (iii) Tecartus (brexucabtagene autoleucel) for R/R mantle-cell lymphoma patients, (iv) Kymriah (tisagenlecleucel) for patients especially peds and young adults suffering with CD19 + R/R B-cell, (v) Yescarta (axicabtagene ciloleucel) specific for refractory large B-cell lymphoma patients. 49 …”

Section: Current Status Of Crispr/cas9 In Cancer Treatmentmentioning

confidence: 99%

“…Based on Cas12a, RPA was introduced as a form of new nucleic acid detection technique named DETECTR which compared with SHERLOCK can eliminate transcription of amplified DNA products into RNA step. 1 – 60 …”

Section: Role Of Crispr/cas9 In Cancer Diagnosis and Treatmentmentioning

confidence: 99%

“…Thus, it can be freely said that CRISPR has its advantages in diagnosis as a personalized, sensitive, and safe monitoring system for cancer patients. 1 – 60 …”

Section: Role Of Crispr/cas9 In Cancer Diagnosis and Treatmentmentioning

confidence: 99%

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RETRACTED: CRISPR/Cas9: A revolutionary genome editing tool for human cancers treatment

Akram

Haq

Sahreen

et al. 2022

Technol Cancer Res Treat

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Cancer is a genetic disease stemming from genetic and epigenetic mutations and is the second most common cause of death across the globe. Clustered regularly interspaced short palindromic repeats (CRISPR) is an emerging gene-editing tool, acting as a defense system in bacteria and archaea. CRISPR/Cas9 technology holds immense potential in cancer diagnosis and treatment and has been utilized to develop cancer disease models such as medulloblastoma and glioblastoma mice models. In diagnostics, CRISPR can be used to quickly and efficiently detect genes involved in various cancer development, proliferation, metastasis, and drug resistance. CRISPR/Cas9 mediated cancer immunotherapy is a well-known treatment option after surgery, chemotherapy, and radiation therapy. It has marked a turning point in cancer treatment. However, despite its advantages and tremendous potential, there are many challenges such as off-target effects, editing efficiency of CRISPR/Cas9, efficient delivery of CRISPR/Cas9 components into the target cells and tissues, and low efficiency of HDR, which are some of the main issues and need further research and development for completely clinical application of this novel gene editing tool. Here, we present a CRISPR/Cas9 mediated cancer treatment method, its role and applications in various cancer treatments, its challenges, and possible solution to counter these challenges.

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Section: Current Status Of Crispr/cas9 In Cancer Treatmentmentioning

confidence: 99%

Section: Role Of Crispr/cas9 In Cancer Diagnosis and Treatmentmentioning

confidence: 99%

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RETRACTED: CRISPR/Cas9: A revolutionary genome editing tool for human cancers treatment

Akram

Haq

Sahreen

et al. 2022

Technol Cancer Res Treat

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“…Clinical trials for the first in vivo application of Cas9 began in 2019 . Presently, CRISPR/Cas9 is used in vast applications in genome editing ranging from therapeutic applications − to plant − and fungal , biotechnology.…”

Section: Discovery and Origin Of The Crispr/cas Systemsmentioning

confidence: 99%

Insights into the Mechanism of CRISPR/Cas9-Based Genome Editing from Molecular Dynamics Simulations

Bhattacharya

Satpati

2022

ACS Omega

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The CRISPR/Cas9 system is a popular genome-editing tool with immense therapeutic potential. It is a simple two-component system (Cas9 protein and RNA) that recognizes the DNA sequence on the basis of RNA:DNA complementarity, and the Cas9 protein catalyzes the double-stranded break in the DNA. In the past decade, near-atomic resolution structures at various stages of the CRISPR/Cas9 DNA editing pathway have been reported along with numerous experimental and computational studies. Such studies have boosted knowledge of the genome-editing mechanism. Despite such advancements, the application of CRISPR/Cas9 in therapeutics is still limited, primarily due to off-target effects. Several studies aim at engineering high-fidelity Cas9 to minimize the off-target effects. Molecular Dynamics (MD) simulations have been an excellent complement to the experimental studies for investigating the mechanism of CRISPR/Cas9 editing in terms of structure, thermodynamics, and kinetics. MD-based studies have uncovered several important molecular aspects of Cas9, such as nucleotide binding, catalytic mechanism, and off-target effects. In this Review, the contribution of MD simulation to understand the CRISPR/Cas9 mechanism has been discussed, preceded by an overview of the history, mechanism, and structural aspects of the CRISPR/Cas9 system. These studies are important for the rational design of highly specific Cas9 and will also be extremely promising for achieving more accurate genome editing in the future.

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“…Similarly, axi-cel, liso-cel, and KTE-X19 also achieved remarkable overall response rates with 83% (5), 73% (6), and 71% (7), respectively. These promising results contribute to the approval of tisagenlecleucel, axicel, liso-cel, and KTE-X19 for r/r B-ALL and/or LBCL (8) (9)(10)(11)(12). Despite these remarkable results of CD19-directed CAR-T therapy compared with traditional chemotherapy (13), it also resulted in serious and even fatal adverse events (AEs).…”

Section: Cd19-targeted Chimeric Antigen Receptor T-cell (Car-t) Thera...mentioning

confidence: 99%

Gastrointestinal infections are underestimated but fatal in chimeric antigen receptor T-cell therapy: a real-world study leveraging FDA adverse event reporting system from 2017 to 2021

Song

Liu

et al. 2022

Preprint

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Clinical trials are underpowered to detect infrequent toxicities following chimeric antigen receptor T-cell (CAR-T) therapy such as gastrointestinal adverse events (GIAEs). Here, we extensively revealed the GIAEs following four U.S. Food and Drug Administration (FDA)-approved CD19-targeted CAR-T products using FDA adverse event reporting system, tisagenlecleucel, axicabtagene-ciloleucel, lisocabtagene maraleucel, and brexucabtagene autoleucel. The disproportionality analyses were performed using reporting odds ratios (ROR) and information component (IC) and the lower bounds of the ROR and IC 95% confidence interval (CI) (ROR025 and IC025) exceeding one and zero were deemed significant, respectively. Among 105,087,611 reports in FAERS between January 2017 and December 2021, 1518 CAR-T-associated GIAEs reports were identified. 23 GIAEs (n = 281, 18.51%) were significantly overreported following CAR-T therapy compared with the full database, of which 11 GIAEs (n = 156, 10.28%) were associated with gastrointestinal infection such as clostridium difficile colitis (n = 44 [2.90%], ROR = 5.55 [95% CI: 4.12-7.46]), enterovirus infection (n = 23 [1.52%], ROR = 20.02 [13.15-30.48]), and mucormycosis (n = 15 [0.99%], ROR = 5.13 [3.09-8.54], all IC025 > 0). Overall, the fatality rate of 11 overreported infection-related GIAEs was 29.49%, which was higher following tisagenlecleucel compared with axicabtagene-ciloleucel (31.45% vs. 24.14%). In this largest post-marketing study to date, we firstly analyzed the CAR-T-associated GIAEs comprehensively and found that gastrointestinal infections were underestimated but led to substantial mortality in CAR-T recipients, which provided a deeper understanding of CAR-T therapy and early alert of those rare but life-threatening GIAEs for the clinician.

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Strengthening the CAR‐T cell therapeutic application using CRISPR/Cas9 technology

Cited by 17 publications

References 110 publications

RETRACTED: CRISPR/Cas9: A revolutionary genome editing tool for human cancers treatment

RETRACTED: CRISPR/Cas9: A revolutionary genome editing tool for human cancers treatment

Insights into the Mechanism of CRISPR/Cas9-Based Genome Editing from Molecular Dynamics Simulations

Gastrointestinal infections are underestimated but fatal in chimeric antigen receptor T-cell therapy: a real-world study leveraging FDA adverse event reporting system from 2017 to 2021

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