Natural killer cell therapy and aerosol interleukin-2 for the treatment of osteosarcoma lung metastasis.
Natural killer cell therapy and aerosol interleukin-2 for the treatment of osteosarcoma lung metastasis.
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DOI：
10.1002/pbc.24801
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发表时间：
2014-04
影响因子：
3.2
通讯作者：
Kleinerman, Eugenie S.
中科院分区：
文献类型：
--
作者：
Guma, Sergei R.;Lee, Dean A.;Yu, Ling;Gordon, Nancy;Hughes, Dennis;Stewart, John;Wang, Wei Lien;Kleinerman, Eugenie S.
骨肉瘤肺转移患者的生存率在20年内没有改善。我们评估了自然杀伤细胞（NK）与气溶胶白细胞介素-2（IL-2）联合应用在转移器官中实现器官特异性NK细胞迁移和扩增以及降低全身性IL-2相关毒性的疗效。分析了5种人骨肉瘤细胞系和103份患者样本（47份原发性和56份转移性）的NKG 2D配体[NKG 2DL]表达。与单独的气溶胶IL-2和没有气溶胶IL-2的NK细胞相比，在体内评价气溶胶IL-2 + NK细胞的治疗功效。骨肉瘤细胞系和患者样品表达不同水平的NKG 2DL。NK介导的杀伤是NKG 2DL依赖性的，并与表达水平相关。气溶胶IL-2增加肺和转移结节内的NK细胞数量，但在其他器官中不增加。根据肿瘤数量、大小和凋亡定量判断，与单独使用NK细胞或气溶胶IL-2相比，治疗效果也有所增加。没有IL-2相关的全身毒性。雾化吸入IL-2可增强NK细胞治疗骨肉瘤肺转移的疗效，而不诱导全身毒性。我们的数据表明，肺部靶向IL-2递送可以避免全身给药引起的毒性。联合应用IL-2气雾剂和NK细胞输注治疗骨肉瘤肺转移可能是一种新的治疗方法。
Survival of patients with osteosarcoma lung metastases has not improved in 20 years. We evaluated the efficacy of combining natural killer [NK] cells with aerosol interleukin-2 [IL-2] to achieve organ-specific NK cell migration and expansion in the metastatic organ, and to decrease toxicity associated with systemic IL-2. Five human osteosarcoma cell lines and 103 patient samples (47 primary and 56 metastatic) were analyzed for NKG2D ligand [NKG2DL] expression. Therapeutic efficacy of aerosol IL-2 + NK cells was evaluated in vivo compared with aerosol IL-2 alone and NK cells without aerosol IL-2. Osteosarcoma cell lines and patient samples expressed various levels of NKG2DL. NK-mediated killing was NKG2DL-dependent and correlated with expression levels. Aerosol IL-2 increased NK cell numbers in the lung and within metastatic nodules but not in other organs. Therapeutic efficacy, as judged by tumor number, size, and quantification of apoptosis, was also increased compared with NK cells or aerosol IL-2 alone. There were no IL-2-associated systemic toxicities. Aerosol IL-2 augmented the efficacy of NK cell therapy against osteosarcoma lung metastasis, without inducing systemic toxicity. Our data suggest that lung-targeted IL-2 delivery circumvents toxicities induced by systemic administration. Combining aerosol IL-2 with NK cell infusions, may be a potential new therapeutic approach for patients with osteosarcoma lung metastasis.
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影响因子：
5.4
作者：
KIESSLING, R;KLEIN, E;WIGZELL, H
通讯作者：
WIGZELL, H
影响因子：
56.9
作者：
Bauer, S;Groh, V;Spies, T
通讯作者：
Spies, T
DOI：
10.1046/j.1359-4117.2002.01003.x
发表时间：
2002-01-01
影响因子：
--
作者：
Jia, Shu-Fang;Zwelling, Leonard A;Kleinerman, Eugene S
通讯作者：
Kleinerman, Eugene S
影响因子：
5.7
作者：
Geryk-Hall M;Yang Y;Hughes DP
通讯作者：
Hughes DP
影响因子：
32.4
作者：
Cosman, D;Müllberg, J;Chalupny, NJ
通讯作者：
Chalupny, NJ