Klingemann Hans
Tufts University Medical School and Conkwest Inc, Cambridge, Massachusetts, USA.
Cytotherapy. 2015 Mar;17(3):245-9. doi: 10.1016/j.jcyt.2014.09.007. Epub 2014 Dec 18.
Natural killer (NK) cells from peripheral or cord blood-especially if they are obtained from a human leukocyte antigen-mismatched (allogeneic) donor-are increasingly being considered for treatment of malignant diseases and to prevent or treat relapse after stem cell transplant. However, in addition to proving their efficacy, there are some more logistical and technical issues that must be addressed before NK cell infusions will be fully accepted by the medical community.
Issues include (i) the expansion of sufficient numbers of cells under conditions suitable, (ii) cryopreservation and (iii) optimization/standardization of shipping conditions if the cells are used at distant sites. Because the patient's own autologous cells usually are not fully functional because of inhibition by "self" major histocompatibility complex expression, better methods must be developed to target NK cells to tumor cells and overcome self-inhibition.
Tumor-directed NK-cell therapy can be best accomplished through genetic engineering of NK cells expressing receptors for tumor antigens or combination with monoclonal antibodies that preferentially kill tumors through antibody-dependent cellular cytotoxicity. If allogeneic NK cells are used, T-lymphocytes in the cell collections that can cause acute graft-versus-host disease in the recipient must be removed.
In addition to showing efficacy in clinical trials, the production of NK cells for treatment must be cost-effective to be eligible for reimbursement by third-party players.
外周血或脐带血中的自然杀伤（NK）细胞——尤其是从人类白细胞抗原不匹配（同种异体）供体获得的NK细胞——越来越多地被考虑用于治疗恶性疾病以及预防或治疗干细胞移植后的复发。然而，除了证明其疗效外，在NK细胞输注被医学界完全接受之前，还有一些后勤和技术问题必须得到解决。
这些问题包括：（i）在合适的条件下扩增足够数量的细胞；（ii）冷冻保存；（iii）如果在远处使用细胞，优化/标准化运输条件。由于患者自身的自体细胞通常因受“自身”主要组织相容性复合体表达的抑制而功能不全，因此必须开发更好的方法，使NK细胞靶向肿瘤细胞并克服自身抑制。
肿瘤导向性NK细胞疗法可以通过对表达肿瘤抗原受体的NK细胞进行基因工程改造，或与通过抗体依赖性细胞毒性优先杀伤肿瘤的单克隆抗体联合使用来最好地实现。如果使用同种异体NK细胞，必须去除细胞制品中可能导致受者发生急性移植物抗宿主病的T淋巴细胞。
除了在临床试验中显示疗效外，用于治疗的NK细胞的生产必须具有成本效益，才有资格获得第三方支付方的报销。
