Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors
By E. Liu, D. Marin, P. Banerjee, H. Macapinlac, P. Thompson, R. Başar, Lucila Nassif kerbauy, Bethany J Overman, Peter F. Thall, Mecit Kaplan and 17 more. New England Journal of Medicine, 2020
1,747 citations recorded by the source corpus.
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 In this phase 1 and 2 trial, we administered HLA-mismatched anti-CD19 CAR-NK cells derived from cord blood to 11 patients with relapsed or refractory CD19-positive cancers (non-Hodgkin’s lymphoma or chronic lymphocytic leukemia [CLL]). NK cells were transduced with a retroviral vector expressing genes that encode anti-CD19 CAR, interleukin-15, and inducible caspase 9 as a safety switch. The cells were expanded ex vivo and administered in a single infusion at one of three doses (1×105, 1×106, or 1×107 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.)
Subfields: Immunology, Oncology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/5f4dfadf44e78b4725129ad60cf6c184a877ce2e
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Immunology
In Oncology
Citations in the corpus
- Cancer Immune Evasion Through Loss of MHC Class I Antigen Presentation (2021, background): “In humans, the level of cytolytic activity of circulating NK cells correlates with the risk of cancer (277) and infiltration of NK cells in some cancers is associated with a better prognosis (278, 279).”