当前位置: X-MOL 学术N. Engl. J. Med. › 论文详情
Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors.
The New England Journal of Medicine ( IF 70.670 ) Pub Date : 2020-02-06 , DOI: 10.1056/nejmoa1910607
Enli Liu,David Marin,Pinaki Banerjee,Homer A Macapinlac,Philip Thompson,Rafet Basar,Lucila Nassif Kerbauy,Bethany Overman,Peter Thall,Mecit Kaplan,Vandana Nandivada,Indresh Kaur,Ana Nunez Cortes,Kai Cao,May Daher,Chitra Hosing,Evan N Cohen,Partow Kebriaei,Rohtesh Mehta,Sattva Neelapu,Yago Nieto,Michael Wang,William Wierda,Michael Keating,Richard Champlin,Elizabeth J Shpall,Katayoun Rezvani

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.).
更新日期:2020-02-06

 

全部期刊列表>>
全球疫情及响应:BMC Medicine专题征稿
欢迎探索2019年最具下载量的化学论文
新版X-MOL期刊搜索和高级搜索功能介绍
化学材料学全球高引用
ACS材料视界
南方科技大学
x-mol收录
南方科技大学
自然科研论文编辑服务
上海交通大学彭文杰
中国科学院长春应化所于聪-4-8
武汉工程大学
课题组网站
X-MOL
深圳大学二维材料实验室张晗
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug