Abstract
Background
Chimeric antigen-receptor T (CAR-T) cells represent great promise in cancer treatment.
CRISPR/Cas9 gene editing in preclinical studies has enabled the development of enhanced
CAR-T products with improved function and reduced toxicity.
Methods
A systematic review of preclinical animal studies was conducted to determine the efficacy
and safety of this approach.
Results
3753 records were identified (to September 9, 2020), with 11 studies using CRISPR/Cas9
gene editing in combination with CAR-T therapy against human cells in animal models
of acute leukemia (four studies), glioma (two studies), melanoma (two studies), and
other cancers (three studies). Compared with unedited controls, gene-edited CAR-T
cells reduced tumor volume in treated animals and improved survival. No adverse side
effects were reported. Use of allogeneic “third-party” CAR-T cells appears feasible.
Improved efficacy was achieved through both knock-in and knockout gene editing of
various targets implicated in immune function. Targeting multiple genes also appears
feasible. Significant heterogeneity in study design and outcome reporting was observed,
and potential bias was identified in all studies.
Conclusion
: CRISPR/Cas9 gene editing enables manufacturing of CAR-T cells with improved anti-cancer
effects. Future studies should reduce unintentional bias and heterogeneity of study
designs and strive to augment long-term persistence of edited cells.
Protocol registration: PROSPERO; registration number CRD42020220313 registered November 30, 2020
Keywords
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Article info
Publication history
Published online: January 14, 2022
Accepted:
October 24,
2021
Received:
August 23,
2021
Footnotes
Disclosures: NK has received honoraria from Gilead and Novartis. DA is a medical consultant with Canadian Blood Services. The authors have no other conflicts of interest to disclose.
Identification
Copyright
© 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.
