Adult peripheral blood and umbilical cord blood NK cells are good sources for effective CAR therapy against CD19 positive leukemic cells

被引:84
作者
Herrera, L. [1 ,6 ]
Santos, S. [1 ,6 ]
Vesga, M. A. [1 ,6 ]
Anguita, J. [2 ,3 ]
Martin-Ruiz, I. [2 ]
Carrascosa, T. [4 ,6 ]
Juan, M. [5 ]
Eguizabal, C. [1 ,6 ]
机构
[1] Basque Ctr Blood Transfus & Human Tissues, Cell Therapy Stem Cells & Tissues Grp, Galdakao, Spain
[2] CIC bioGUNE, Macrophage & Tick Vaccine Lab, Derio, Biscay, Spain
[3] Basque Fdn Sci, Ikerbasque, Bilbao, Biscay, Spain
[4] Hosp Galdakao Usansolo, Serv Hematol, Galdakao, Spain
[5] Univ Barcelona, Hosp Clin Barcelona, Inst Invest Biomed August Pi i Sunyer Hosp, Hosp St Joan Deu,Serve Immunol, Barcelona, Spain
[6] Biocruces Bizkaia Hlth Res Inst, Baracaldo, Spain
关键词
NATURAL-KILLER-CELLS; EX-VIVO EXPANSION; T-CELLS; B-CELL; NK-92; CELLS; IMMUNOTHERAPY; TRANSPLANTATION; ACTIVATION; RECEPTORS; SAFETY;
D O I
10.1038/s41598-019-55239-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Among hematological cancers, Acute Lymphoblastic Leukemia (ALL) and Chronic Lymphocytic Leukemia (CLL) are the most common leukemia in children and elderly people respectively. Some patients do not respond to chemotherapy treatments and it is necessary to complement it with immunotherapy-based treatments such as chimeric antigen receptor (CAR) therapy, which is one of the newest and more effective treatments against these cancers and B-cell lymphoma. Although complete remission results are promising, CART cell therapy presents still some risks for the patients, including cytokine release syndrome (CRS) and neurotoxicity. We proposed a different immune cell source for CAR therapy that might prevent these side effects while efficiently targeting malignant cells. NK cells from different sources are a promising vehicle for CAR therapy, as they do not cause graft versus host disease (GvHD) in allogenic therapies and they are prompt to attack cancer cells without prior sensitization. We studied the efficacy of NK cells from adult peripheral blood (AB) and umbilical cord blood (CB) against different target cells in order to determine the best source for CAR therapy. AB CAR-NK cells are slightly better at killing CD19 presenting target cells and CB NK cells are easier to stimulate and they have more stable number from donor to donor. We conclude that CAR-NK cells from both sources have their advantages to be an alternative and safer candidate for CAR therapy.
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页数:10
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