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Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors
Open accessAbstract
BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in B-cell cancers. However, CAR T cells can induce substantial toxic effects, and the manufacture of the cells is complex. Natural killer (NK) cells that have been modified to express an anti-CD19 CAR have the potential to overcome these limitations. METHODS: CAR-NK cells per kilogram of body weight) after lymphodepleting chemotherapy. RESULTS: The administration of CAR-NK cells was not associated with the development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, and there was no increase in the levels of inflammatory cytokines, including interleukin-6, over baseline. The maximum tolerated dose was not reached. Of the 11 patients who were treated, 8 (73%) had a response; of these patients, 7 (4 with lymphoma and 3 with CLL) had a complete remission, and 1 had remission of the Richter's transformation component but had persistent CLL. Responses were rapid and seen within 30 days after infusion at all dose levels. The infused CAR-NK cells expanded and persisted at low levels for at least 12 months. CONCLUSIONS: Among 11 patients with relapsed or refractory CD19-positive cancers, a majority had a response to treatment with CAR-NK cells without the development of major toxic effects. (Funded by the M.D. Anderson Cancer Center CLL and Lymphoma Moonshot and the National Institutes of Health; ClinicalTrials.gov number, NCT03056339.).
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“The trial in adults with chronic lymphocytic leukemia demonstrated that CAR-NK targeting CD19 are safe and effective [143].”
From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [143]
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“However, the results from studies on targets other than CD19 in CAR-NK have been less than satisfactory, including both in vivo studies and clinical research.”
From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [143]
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“In a recent study of NK-cell CAR therapy, there were no reported cases of cytokine storm or even elevated interleukin-6 levels,60”
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Metadata
- Authors
- Liu, E., Marin, D., Banerjee, P., Macapinlac, H. A., Thompson, P., Basar, R., Nassif Kerbauy, L., Overman, B., Thall, P., Kaplan, M., Nandivada, V., Kaur, I., Nunez Cortes, A., Cao, K., Daher, M., Hosing, C., Cohen, E. N., Kebriaei, P., Mehta, R., Neelapu, S., Nieto, Y., Wang, M., Wierda, W., Keating, M., Champlin, R., Shpall, E. J., & Rezvani, K.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- From the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, Houston.
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2020-02-06
- Volume
- 382
- Issue
- 6
- Pages
- 545-553
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC7101242
- OpenAlex
- W3004611567
- Cited by
- 2,217
- References
- 37
- Citations by year
- 2026: 282 · 2025: 337 · 2024: 332 · 2023: 323 · 2022: 353 · 2021: 379 · 2020: 205
- FWCI
- 113.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- M.D. Anderson Cancer Center CLL and lymphoma Moonshot Grants
- National Institutes of Health (1 R01 CA211044-01, 5P01CA148600-03, CA016672, P50CA100632-16)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- CAR-NK cells, chimeric antigen receptor, natural killer cells, anti-CD19, relapsed or refractory B-cell lymphoma, chronic lymphocytic leukemia, Richter transformation, lymphodepleting chemotherapy, cytokine release syndrome, neurotoxicity, graft-versus-host disease, interleukin-6, CAR T-cell toxicity
- MeSH terms
- Receptors, Chimeric Antigen, Aged, Female, Fetal Blood, Genetic Vectors, Humans, Killer Cells, Natural, Lymphoma, Non-Hodgkin, Male, Middle Aged, Remission Induction, Retroviridae, Leukemia, Lymphocytic, Chronic, B-Cell, Antigens, CD19, Transplantation Conditioning, Allografts, Cell- and Tissue-Based Therapy
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