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Deleting DNMT3A in CAR T cells prevents exhaustion and enhances antitumor activity
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DNMT3A deletion preserves CAR T cell functionality during prolonged stimulation.
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“Another study evaluated the effect of DNMT3A loss on CAR-T cells and showed that these cells had an increased ability to proliferate without acquiring a canonical exhaustion phenotype in the context of chronic stimulation [79].”
From Clonal hematopoiesis and inflammation – the perpetual cycle (2023) · cites this paper as [79]
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Park, J. H., Rivière, I., Gonen, M., Wang, X., Sénéchal, B., Curran, K. J., Sauter, C., Wang, Y., Santomasso, B., Mead, E., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1709919 · Cited by 2,688
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Metadata
- Authors
- Prinzing, B., Zebley, C. C., Petersen, C. T., Fan, Y., Anido, A. A., Yi, Z., Nguyen, P., Houke, H., Bell, M., Haydar, D., Brown, C., Boi, S. K., Alli, S., Crawford, J. C., Riberdy, J. M., Park, J. J., Zhou, S., Velasquez, M. P., DeRenzo, C., Lazzarotto, C. R., Tsai, S. Q., Vogel, P., Pruett-Miller, S. M., Langfitt, D. M., Gottschalk, S., Youngblood, B., & Krenciute, G.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Department of Hematology, St Jude Children’s Research Hospital, Memphis, TN 38105, USA.
- Department of Cell and Molecular Biology, St Jude Children’s Research Hospital, Memphis, TN 38105, USA.
- Corresponding author
- Prinzing, Brooke
- Zebley, Caitlin C.
- Petersen, Christopher T.
- Gottschalk, Stephen
- Youngblood, Ben
- Krenciute, Giedre
- ORCID
- Prinzing, Brooke
- Zebley, Caitlin C.
- Fan, Yiping
- Anido, Alejandro Allo
- Yi, Zhongzhen
- Nguyen, Phuong
- Houke, Haley
- Bell, Matthew
- Haydar, Dalia
- Brown, Charmaine
- Boi, Shannon K.
- Alli, Shanta
- Crawford, Jeremy Chase
- Riberdy, Janice M.
- Park, Jeoungeun J.
- Zhou, Sheng
- Velasquez, Mireya Paulina
- DeRenzo, Chris
- Lazzarotto, Cicera R.
- Tsai, Shengdar Q.
- Vogel, Peter
- Pruett-Miller, Shondra M.
- Langfitt, Deanna M.
- Gottschalk, Stephen
- Youngblood, Ben
- Krenciute, Giedre
- Venue
- Science Translational Medicine
- Published
- 2021-11-17
- Volume
- 13
- Issue
- 620
- Pages
- eabh0272-eabh0272
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC8733956
- OpenAlex
- W3213155546
- Cited by
- 349
- References
- 84
- Citations by year
- 2026: 68 · 2025: 78 · 2024: 83 · 2023: 82 · 2022: 37 · 2021: 1
- FWCI
- 18.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R50CA211481, K99CA256262, F31CA250401, R01CA173750, R00CA256262, P01CA096832, P30CA021765, R01CA237311)
- National Institute of Allergy and Infectious Diseases (R01AI114442, U01AI157189, UM1AI109565)
- National Institute of Neurological Disorders and Stroke (R01NS106379, R01NS121249)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- CAR T-cell therapy, T cell exhaustion, DNMT3A, DNA methylation, epigenetic repression, IL-10, CD28, CCR7, TCF1, LEF1, antitumor immunity, T cell stemness, epigenetic silencing
- MeSH terms
- Humans, Neoplasms, T-Lymphocytes, Immunotherapy, Adoptive, CD28 Antigens, Xenograft Model Antitumor Assays, Epigenesis, Genetic
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