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Cited by 659CAR-T cell therapy researchImmunotherapy and Immune ResponsesCRISPR and Genetic Engineering

Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell

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Ruella, Marco, Xu, Jun, Barrett, David M., Fraietta, Joseph A., Reich, Tyler J., Ambrose, David E., Klichinsky, Michael, Shestova, Olga +18 more·2018·Nature Medicine
DOI 10.1038/s41591-018-0201-9PMC PMC6511988
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Abstract

We report a patient relapsing 9 months after CD19-targeted CAR T cell (CTL019) infusion with CD19- leukemia that aberrantly expressed the anti-CD19 CAR. The CAR gene was unintentionally introduced into a single leukemic B cell during T cell manufacturing, and its product bound in cis to the CD19 epitope on the surface of leukemic cells, masking it from recognition by and conferring resistance to CTL019.

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Crossref · 10.1038/s41591-018-0201-9

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  • Transduction of cells other than T lymphocytes, such as malignant blasts, has been observed, creating the risk of engineering CARs into cancer cells and giving rise to CAR-resistant tumor cells.

    “Further, transduction of cells other than T lymphocytes (e.g. malignant blasts) has been observed, creating the risk of engineering CARs into cancer cells, giving rise to CAR-resistant tumor cells (48).”

    From Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy (2021) · cites this paper as [48]

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Research works printed but not linked: 34

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Authors
Ruella, M., Xu, J., Barrett, D. M., Fraietta, J. A., Reich, T. J., Ambrose, D. E., Klichinsky, M., Shestova, O., Patel, P. R., Kulikovskaya, I., Nazimuddin, F., Bhoj, V. G., Orlando, E. J., Fry, T. J., Bitter, H., Maude, S. L., Levine, B. L., Nobles, C. L., Bushman, F. D., Young, R. M., Scholler, J., Gill, S. I., June, C. H., Grupp, S. A., Lacey, S. F., & Melenhorst, J. J.
Affiliations
  • Abramson Cancer Center (US)
  • Children's Hospital of Philadelphia (US)
  • University of Pennsylvania (US)
  • Children's Hospital Colorado (US)
Corresponding author
  • June, Carl H.
  • Melenhorst, J. Joseph
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2018-10
Volume
24
Issue
10
Pages
1499-1503
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/s41591-018-0201-9
PMC
PMC6511988
OpenAlex
W2893691711
Cited by
659
References
36
Citations by year
2026: 61 · 2025: 73 · 2024: 83 · 2023: 84 · 2022: 83 · 2021: 91 · 2020: 91 · 2019: 78 · 2018: 14 · 2012: 1
FWCI
25.75
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (K99CA212302, R00CA212302, T32CA009140, R01CA120409, P01CA214278)
Topics
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
Keywords
CAR T-cell therapy, CD19, tisagenlecleucel, B-cell acute lymphoblastic leukemia, CAR T cell manufacturing, relapse
MeSH terms
Receptors, Chimeric Antigen, Adult, Epitopes, B-Lymphocytes, Humans, Leukemia, Male, Receptors, Antigen, T-Cell, T-Lymphocytes, Antigens, CD19, Drug Resistance, Neoplasm, Young Adult, Cell- and Tissue-Based Therapy

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