Hydrodynamic delivery of human IL-15 cDNA increases murine natural killer cell recovery after syngeneic bone marrow transplantation.
Hydrodynamic delivery of human IL-15 cDNA increases murine natural killer cell recovery after syngeneic bone marrow transplantation.
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DOI：
10.1016/j.bbmt.2011.08.023
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发表时间：
2011-12
影响因子：
4.3
通讯作者：
Murphy, William J.
中科院分区：
文献类型：
--
作者：
Barao, Isabel;Alvarez, Maite;Redelman, Doug;Weiss, Jonathan M.;Ortaldo, John R.;Wiltrout, Robert H.;Murphy, William J.
骨髓移植（BMT）后立即出现的免疫缺陷增加了机会性感染和肿瘤复发的易感性。自然杀伤细胞（NK）在抵抗病毒感染和转化细胞中起着重要的作用。IL-15已被证明对NK细胞的发育和存活至关重要。我们将人IL-15 cDNA （IL-15）通过流体动力学传递给接受基因BMT的小鼠受体，以确定其对NK细胞重建的影响。液体动力给药可导致血清中高水平的il -15蛋白持续数天，然后迅速下降。hIL-15出现后，受体的骨髓、脾脏和肝脏内成熟的供体来源NK细胞显著增加。未观察到未成熟NK细胞祖细胞的积累。来自IL-15处理的受体的NK细胞显示出激活的表型，并且在体外对肿瘤靶点具有相似的裂解活性，其程度与来自对照质粒处理的受体的细胞相似。这表明IL-15的主要作用是NK细胞总数的定量增加，而不是NK细胞功能的质变。未观察到任何毒副作用。在携带肾癌肿瘤的移植小鼠中进行的研究表明，这种hIL-15基因传递模式导致抗肿瘤反应增强。这些结果支持使用基于细胞因子基因转移的方案作为增强BMT后NK细胞恢复的平台。
Immune deficiency immediately following bone marrow transplantation (BMT) increases susceptibility to opportunistic infections as well as tumor relapse. Natural Killer (NK) cells play important roles in the resistance to virally infected and transformed cells. IL-15 has been shown to be essential for NK cell development and survival. We administered human (h) IL-15 cDNA (pIL-15) via hydrodynamic delivery to murine recipients undergoing congenic BMT to determine its effects on NK cell reconstitution. Hydrodynamic pIL-15 delivery resulted in high levels of hIL-15 protein in the serum which lasted for several days and then quickly declined. The appearance of hIL-15 was followed by a significant increase of mature donor-derived NK cells within the bone marrow, spleens and livers of the treated recipients. No accumulation of immature NK cell progenitors was observed. The NK cells from IL-15 treated recipients displayed an activated phenotype and were lytically active towards tumor targets in vitro to a similar degree as did those cells from recipients treated with control plasmid. This suggests that the predominant effect of IL-15 was a quantitative increase in total NK cell numbers and not qualitative changes in NK cell functions. No toxicities or adverse effects were observed. Studies performed in transplanted mice bearing renal carcinoma tumors demonstrated that this mode of hIL-15 gene delivery resulted in increased anti-tumor responses. These results support the use of cytokine gene transfer-based regimens as a platform to augment NK cell recovery after BMT.
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影响因子：
39.2
作者：
MARKS, DI;CULLIS, JO;GOLDMAN, JM
通讯作者：
GOLDMAN, JM
影响因子：
4.4
作者：
Pillet, Anne-Helene;Bugault, Florence;Rose, Thierry
通讯作者：
Rose, Thierry
影响因子：
2.6
作者：
McCullar, Valarie;Oostendorp, Robert;Miller, Jeffrey S.
通讯作者：
Miller, Jeffrey S.
DOI：
10.1084/jem.191.5.771
发表时间：
2000-03-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kennedy MK;Glaccum M;Brown SN;Butz EA;Viney JL;Embers M;Matsuki N;Charrier K;Sedger L;Willis CR;Brasel K;Morrissey PJ;Stocking K;Schuh JC;Joyce S;Peschon JJ
通讯作者：
Peschon JJ
DOI：
10.4049/jimmunol.0900719
发表时间：
2009-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Castillo EF;Stonier SW;Frasca L;Schluns KS
通讯作者：
Schluns KS