Anti-myeloma activity of endogenous and adoptively transferred activated natural killer cells in experimental multiple myeloma model
Anti-myeloma activity of endogenous and adoptively transferred activated natural killer cells in experimental multiple myeloma model
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DOI：
10.1016/j.exphem.2007.08.006
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发表时间：
2007-12-01
影响因子：
2.6
通讯作者：
Dilber, M. Sirac
中科院分区：
文献类型：
--
作者：
Alici, Evren;Konstantinidis, Kyriakos V.;Dilber, M. Sirac
目标。尽管在自体干细胞移植和化疗方面取得了进展，但多发性骨髓瘤(MM)仍然是一种不治之症。由于自然杀伤(NK)细胞在宿主抵抗多种肿瘤中的作用，探讨NK细胞的抗MM活性是很有意义的。为此，我们的目的是确定NK细胞在注射白介素2(IL-2)后是否具有抗MM的活性，以及体外激活和静脉注射NK细胞是否延长了荷瘤C57BL/KaLwRij小鼠的生存时间。用小鼠腹腔注射IL-2的方法检测IL-2对5T33 MM的抗MM作用。随后，通过注射抗NK1.1或抗CD8单抗进行体内效应细胞去除。最后，将从C57BL/KaLwRij小鼠脾细胞中分离并激活的NK细胞过继转移到荷瘤小鼠体内，并结合IL-2治疗。IL-2可显著延长荷瘤小鼠的存活时间。这种作用因体内NK细胞的耗尽而减弱。过继转移活化的NK细胞具有明显的体内抗MM作用，且呈细胞剂量依赖关系。标记过继转移的NK细胞的生物分布与MM细胞的归巢部位有关。这些数据表明，激活的NK细胞在MM的过继免疫治疗中有很大的潜力。(C)2007 ISEH-血液和干细胞学会。由爱思唯尔公司出版。
Objective. Despite advances in autologous stem cell transplantation and chemotherapy, multiple myeloma (MM) remains an incurable disease. Due to the role of natural killer (NK) cells in host resistance against several tumors, it is of interest to explore the anti-MM activity of NK cells. For this reason, we aimed to determine if NK cells provide anti-MM activity following interleukin-2 (IL-2) administration, and if ex vivo activated and intravenously administered NK cells prolong survival in MM-bearing C57BL/KaLwRij mice.Methods. The anti-MM effect of IL-2 was tested by intraperitoneal injection into the 5T33MM-inoculated mice. Subsequently, in vivo effector cell depletions were performed by administration of anti-NK1.1 or anti-CD8 monoclonal antibodies. Finally, magnetically separated and activated NK cells from splenocytes of C57BL/KaLwRij mice were adoptively transferred to tumor-bearing mice in conjunction with IL-2 treatment.Results. IL-2 administration into MM-bearing mice significantly prolonged their survival. This effect was diminished by in vivo depletion of NK cells. Adoptive transfer of activated NK cells showed a significant in vivo anti-MM effect that was dependent on cell dose. Biodistribution of the marked adoptively transferred NK cells correlated with MM cells' homing sites.Conclusion. These data suggest that activated NK cells have a promising potential in adoptive immunotherapy for MM. (C) 2007 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.