Cited by 2,217CAR-T cell therapy researchImmune Cell Function and InteractionImmunotherapy and Immune Responses

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Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors

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Liu, Enli, Marin, David, Banerjee, Pinaki, Macapinlac, Homer A., Thompson, Philip, Basar, Rafet, Nassif Kerbauy, Lucila, Overman, Bethany, Thall, Peter, Kaplan, Mecit, Nandivada, Vandana, Kaur, Indresh, Nunez Cortes, Ana, Cao, Kai, Daher, May, Hosing, Chitra, Cohen, Evan N., Kebriaei, Partow, Mehta, Rohtesh, Neelapu, Sattva, Nieto, Yago, Wang, Michael, Wierda, William, Keating, Michael, Champlin, Richard, Shpall, Elizabeth J., Rezvani, Katayoun·2020·New England Journal of Medicine

DOI 10.1056/nejmoa1910607PMC PMC7101242

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Abstract

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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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: Liu, Enli
Banerjee, Pinaki
Macapinlac, Homer A.
Thompson, Philip
Thall, Peter
Kaplan, Mecit
Cao, Kai
Daher, May
Hosing, Chitra
Cohen, Evan N.
Kebriaei, Partow
Mehta, Rohtesh
Neelapu, Sattva
Nieto, Yago
Wang, Michael
Wierda, William
Keating, Michael
Champlin, Richard
Shpall, Elizabeth J.
Rezvani, Katayoun
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
DOI: 10.1056/nejmoa1910607
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
Licence: www.nejmgroup.org/legal/terms-of-use.htm (vor)
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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Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors

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