Replication-Competent Retroviruses in Gene-Modified T Cells Used in Clinical Trials: Is It Time to Revise the Testing Requirements?
Open accessAbstract
Adoptive T-cell transfer is recognized as an innovative treatment strategy for various malignant diseases.1,2 To improve the efficacy and sometimes the safety of this approach, T cells can be genetically manipulated to modify their antigen specificity, to enhance their in vivo survival and trafficking to specific tissues, or to be eliminated in the event of undesired toxic effects.3 γ-retroviral vectors are frequently used to obtain robust and stable genetic modification of human T lymphocytes because these vectors can efficiently integrate within the genome and ensure that the inserted transgene is passed to the progeny of infected cells.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In therapies using gammaretroviral or lentiviral vectors, there is a theoretical potential for recombination events during vector manufacturing that result in replication-competent retroviruses or lentiviruses (RCRs/RCLs).
“In therapies using either gammaretroviral or lentiviral vectors, there is a theoretical potential for recombination events to occur during vector manufacturing that result in replication-competent retroviruses or lentiviruses (RCRs/RCLs) [82].”
From Clinical use of lentiviral vectors (2018) · cites this paper as [82]
The US FDA, European Medicines Agency, and most regulatory agencies require extensive testing for RCRs/RCLs in vector products as well as in patients.
“Therefore, the US Food and Drug Administration (FDA), the European Medicines Agency, and most regulatory agencies require extensive testing for RCRs/RCLs in vector products as well as in patients [82, 83].”
From Clinical use of lentiviral vectors (2018) · cites this paper as [82]
Cites
A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency
Hacein-Bey-Abina, S., von Kalle, C., Schmidt, M., Le Deist, F., Wulffraat, N., McIntyre, E., Radford, I., Villeval, J.-L., Fraser, C. C., Cavazzana-Calvo, M., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejm200301163480314 · Cited by 1,867 · see citing works
Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer
Donahue, R. E., Kessler, S. W., Bodine, D., McDonagh, K., Dunbar, C., Goodman, S., Agricola, B., Byrne, E., Raffeld, M., & Moen, R. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.176.4.1125 · Cited by 532 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Clinical use of lentiviral vectors
Milone, M. C., & O’Doherty, U. (2018) · Leukemia · doi:10.1038/s41375-018-0106-0 · Cited by 930 · see citing works
“Patients can be monitored for RCRs/RCLs through polymerase chain reaction or serological assays, and the FDA suggests that patients be monitored for recombinant virus every 3 months for the first year after receiving gene therapy.”
BackgroundInfluentialGlobal Manufacturing of CAR T Cell Therapy
Levine, B. L., Miskin, J., Wonnacott, K., & Keir, C. (2017) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2016.12.006 · Cited by 765 · see citing works
Genetically Modified T-Cell Therapy for Osteosarcoma: Into the Roaring 2020s
DeRenzo, C., & Gottschalk, S. (2020) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-030-43032-0_10 · Cited by 12 · see citing works
- Authors
- Bear, A. S., Morgan, R. A., Cornetta, K., June, C. H., Binder-Scholl, G., Dudley, M. E., Feldman, S. A., Rosenberg, S. A., Shurtleff, S. A., Rooney, C. M., Heslop, H. E., & Dotti, G.
- Affiliations
- Houston Methodist (US)
- National Cancer Institute (US)
- Indiana University Indianapolis (US)
- Abramson Cancer Center (US)
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Dotti, Gianpietro
- ORCID
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 20
- Issue
- 2
- Pages
- 246-249
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC3277217
- OpenAlex
- W2079240923
- Cited by
- 59
- References
- 2
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 6 · 2017: 5 · 2016: 1 · 2015: 5 · 2014: 5 · 2013: 8 · 2012: 2
- FWCI
- 3.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Leukemia and Lymphoma Society
- National Institutes of Health
- National Heart, Lung, and Blood Institute (U54HL081007, P40HL116242, T32HL092332)
- National Cancer Institute (P01CA094237, P50CA126752)
- National Center for Research Resources (P40RR024928)
- 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 › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- genetically modified T cells, adoptive T cell therapy, gammaretroviral vectors, clinical trial requirements, retroviral integration
- MeSH terms
- Animals, Cell Line, Clinical Trials as Topic, Genetic Vectors, Humans, Retroviridae, T-Lymphocytes, Transduction, Genetic, Virus Replication, Genetic Therapy, Toxicity Tests
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
