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Cited by 98Virus-based gene therapy researchCAR-T cell therapy researchRNA Interference and Gene Delivery

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Absence of Replication-Competent Lentivirus in the Clinic: Analysis of Infused T Cell Products

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Cornetta, Kenneth, Duffy, Lisa, Turtle, Cameron J., Jensen, Michael, Forman, Stephen, Binder-Scholl, Gwendolyn, Fry, Terry, Chew, Anne, Maloney, David G., June, Carl H.·2018·Molecular Therapy
DOI 10.1016/j.ymthe.2017.09.008PMC PMC5762981
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Abstract

Exposure to replication-competent lentivirus (RCL) is a theoretical safety concern for individuals treated with lentiviral gene therapy. For certain ex vivo gene therapy applications, including cancer immunotherapy trials, RCL detection assays are used to screen the vector product as well as the vector-transduced cells. In this study, we reviewed T cell products screened for RCL using methodology developed in the National Gene Vector Biorepository. All trials utilized third-generation lentiviral vectors produced by transient transfection. Samples from 26 clinical trials totaling 460 transduced cell products from 375 subjects were evaluated. All cell products were negative for RCL. A total of 296 of the clinical trial participants were screened for RCL at least 1 month after infusion of the cell product. No research subject has shown evidence of RCL infection. These findings provide further evidence attesting to the safety of third-generation lentiviral vectors and that testing T cell products for RCL does not provide added value to screening the lentiviral vector product.

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Metadata

Authors
Cornetta, K., Duffy, L., Turtle, C. J., Jensen, M., Forman, S., Binder-Scholl, G., Fry, T., Chew, A., Maloney, D. G., & June, C. H.
Affiliations
  • Indiana University Indianapolis (US)
  • Indiana University School of Medicine (US)
  • University of Washington (US)
  • City Of Hope National Medical Center (US)
  • National Institutes of Health (US)
  • University of Pennsylvania (US)
Corresponding author
Cornetta, Kenneth
ORCID
Venue
Molecular Therapy
Publisher
Elsevier BV
Published
2018-01
Volume
26
Issue
1
Pages
280-288
ISSN
1525-0016 (ISSN-L)
DOI
10.1016/j.ymthe.2017.09.008
PMC
PMC5762981
OpenAlex
W2756236961
Cited by
98
References
5
Citations by year
2026: 3 · 2025: 9 · 2024: 11 · 2023: 7 · 2022: 14 · 2021: 9 · 2020: 16 · 2019: 15 · 2018: 12
FWCI
8.17
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Therapy (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
Funders
  • NHLBI (P40HL1162, 4, 2, NCT01865617)
  • Intramural Research Program at the NIH
  • Juno Therapeutics
  • Novartis
  • University of Pennsylvania
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
lentiviral gene therapy, ex vivo gene therapy, transient transfection, cancer immunotherapy
MeSH terms
Cell Line, Follow-Up Studies, Genetic Vectors, Humans, T-Lymphocytes, Transduction, Genetic, Virus Replication, Genetic Therapy, Lentivirus, Adoptive Transfer

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