Alici Evren, Sutlu Tolga, Björkstrand Bo, Gilljam Mari, Stellan Birgitta, Nahi Hareth, Quezada Hernan Concha, Gahrton Gösta, Ljunggren Hans-Gustaf, Dilber M Sirac
Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Blood. 2008 Mar 15;111(6):3155-62. doi: 10.1182/blood-2007-09-110312. Epub 2008 Jan 11.
Multiple myeloma (MM) is an incurable plasma cell malignancy with poor outcome. The most promising therapeutic options currently available are combinations of transplantation, targeted pharmacotherapy, and immunotherapy. Cell-based immunotherapy after hematopoietic stem-cell transplantation has been attempted, but with limited efficacy. Natural killer (NK) cells are interesting candidates for new means of immunotherapy; however, their potential clinical use in MM has not been extensively studied. Here, we explored the possibility of expanding NK cells from the peripheral blood of 7 newly diagnosed, untreated MM patients, using good manufacturing practice (GMP)-compliant components. After 20 days of culture, the number of NK cells from these patients had expanded on average 1600-fold. Moreover, expanded NK cells showed significant cytotoxicity against primary autologous MM cells, yet retained their tolerance against nonmalignant cells. Based on these findings, we propose that autologous NK cells expanded ex vivo deserve further attention as a possible new treatment modality for MM.
多发性骨髓瘤(MM)是一种无法治愈的浆细胞恶性肿瘤,预后较差。目前最有前景的治疗选择是移植、靶向药物治疗和免疫治疗的联合应用。造血干细胞移植后的细胞免疫治疗已被尝试,但疗效有限。自然杀伤(NK)细胞是免疫治疗新方法的有趣候选者;然而,它们在MM中的潜在临床应用尚未得到广泛研究。在此,我们探讨了使用符合药品生产质量管理规范(GMP)的成分从7例新诊断、未治疗的MM患者外周血中扩增NK细胞的可能性。培养20天后,这些患者的NK细胞数量平均扩增了1600倍。此外,扩增后的NK细胞对原发性自体MM细胞显示出显著的细胞毒性,但对非恶性细胞仍保持耐受性。基于这些发现,我们提出,体外扩增的自体NK细胞作为MM可能的新治疗方式值得进一步关注。