Treatment of patients with advanced cancer with the natural killer cell line NK-92

淋巴瘤 淋巴因子激活杀伤细胞 自然杀伤细胞 免疫学 细胞毒性T细胞 抗体 癌症研究 癌症 CD3型 医学 免疫系统 生物 白细胞介素21 内科学 T细胞 CD8型 体外 生物化学
作者
Torsten Tonn,Dirk Schwabe,Hans Klingemann,Sven Becker,Ruth Esser,Ulrike Koehl,Meinolf Suttorp,Erhard Seifried,Oliver G. Ottmann,Gesine Bug
出处
期刊:Cytotherapy [Elsevier]
卷期号:15 (12): 1563-1570 被引量:398
标识
DOI:10.1016/j.jcyt.2013.06.017
摘要

Background aims Natural killer (NK) cells, either naive or genetically engineered, are increasingly considered for cellular therapy of patients with malignancies. When using NK cells from peripheral blood, the number of expanded NK cells can be highly variable and the need for NK cell enrichment can make the process expensive. The NK-92 cell line (CD56+/CD3−) that was isolated from a patient with lymphoma has predictable high cytotoxic activity and can be expanded under good manufacturing practice conditions in recombinant interleukin-2. Methods Fifteen patients (age, 9–71 years) with advanced, treatment-resistant malignancies, either solid tumors/sarcomas (n = 13) or leukemia/lymphoma (n = 2), received two infusions of NK-92 cells, given 48 h apart. Three cohorts of patients were treated with escalating doses of NK-92 cells (n = 7 at 1 × 109, n = 6 at 3 × 109 and n = 2 at 1 × 1010 cells/m2). Results No infusion-related or long-term side effects were observed. The dose of 1010 cells/m2 was considered the maximum expandable cell dose with the use of an established culture bag system. Three fourths of patients with lung cancer had some anti-tumor response. Only one patient of seven had development of human leukocyte antigen antibodies. The persistence of NK-92 cells (male origin) in the circulation was confirmed by Y chromosome–specific polymerase chain reaction in two female patients. Conclusions Infusions of NK-92 cells up to 1010 cells/m2 were well tolerated. Despite the allogeneic nature of NK-92, development of human leukocyte antigen antibodies in these patients with cancer appears to be rare. The cells can persist in the recipient's circulation for at least 48 h. Some encouraging responses were seen in patients with advanced lung cancer.
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