| GeneLibs

题目:: Continuously expanding CAR NK-92 cells display selective cytotoxicity against B-cell leukemia and lymphoma.
作者:: Oelsner(Sarah),Friede(Miriam E),Zhang(Congcong),Wagner(Juliane),Badura(Susanne),Bader(Peter),Ullrich(Evelyn),Ottmann(Oliver G),Klingemann(Hans),Tonn(Torsten),Wels(Winfried S)
状态:: 发布时间2016-11-26 , 更新时间 2016-11-27
期刊:: Cytotherapy
摘要:: Natural killer (NK) cells can rapidly respond to transformed and stressed cells and represent an important effector cell type for adoptive immunotherapy. In addition to donor-derived primary NK cells, continuously expanding cytotoxic cell lines such as NK-92 are being developed for clinical applications.,To enhance their therapeutic utility for the treatment of B-cell malignancies, we engineered NK-92 cells by lentiviral gene transfer to express chimeric antigen receptors (CARs) that target CD19 and contain human CD3ζ (CAR 63.z), composite CD28-CD3ζ or CD137-CD3ζ signaling domains (CARs 63.28.z and 63.137.z).,Exposure of CD19-positive targets to CAR NK-92 cells resulted in formation of conjugates between NK and cancer cells, NK-cell degranulation and selective cytotoxicity toward established B-cell leukemia and lymphoma cells. Likewise, the CAR NK cells displayed targeted cell killing of primary pre-B-ALL blasts that were resistant to parental NK-92. Although all three CAR NK-92 cell variants were functionally active, NK-92/63.137.z cells were less effective than NK-92/63.z and NK-92/63.28.z in cell killing and cytokine production, pointing to differential effects of the costimulatory CD28 and CD137 domains. In a Raji B-cell lymphoma model in NOD-SCID IL2R γ mice, treatment with NK-92/63.z cells, but not parental NK-92 cells, inhibited disease progression, indicating that selective cytotoxicity was retained in vivo.,Our data demonstrate that it is feasible to generate CAR-engineered NK-92 cells with potent and selective antitumor activity. These cells may become clinically useful as a continuously expandable off-the-shelf cell therapeutic agent.
语言:: eng
DOI:: 10.1016/j.jcyt.2016.10.009

文献库文献相关信息

DataTable pData

联系方式

微信公众号

文献库 文献相关信息

DataTable pData

联系方式

微信公众号

文献库文献相关信息