Klingemann Hans, Boissel Laurent, Toneguzzo Frances
NantKwest, Inc. , Culver City, CA , USA.
Front Immunol. 2016 Mar 14;7:91. doi: 10.3389/fimmu.2016.00091. eCollection 2016.
Natural killer (NK) cells are potent cytotoxic effector cells for cancer therapy and potentially for severe viral infections. However, there are technical challenges to obtain sufficient numbers of functionally active NK cells from a patient's blood since they represent only 10% of the lymphocytes and are often dysfunctional. The alternative is to obtain cells from a healthy donor, which requires depletion of the allogeneic T cells to prevent graft-versus-host reactions. Cytotoxic cell lines have been established from patients with clonal NK-cell lymphoma. Those cells can be expanded in culture in the presence of IL-2. Except for the NK-92 cell line, though, none of the other six known NK cell lines has consistently and reproducibly shown high antitumor cytotoxicity. Only NK-92 cells can easily be genetically manipulated to recognize specific tumor antigens or to augment monoclonal antibody activity through antibody-dependent cellular cytotoxicity. NK-92 is also the only cell line product that has been infused into patients with advanced cancer with clinical benefit and minimal side effects.
自然杀伤(NK)细胞是用于癌症治疗以及可能用于治疗严重病毒感染的强效细胞毒性效应细胞。然而,从患者血液中获取足够数量的功能活跃的NK细胞存在技术挑战,因为它们仅占淋巴细胞的10%,且常常功能失调。另一种方法是从健康供体获取细胞,这需要去除同种异体T细胞以防止移植物抗宿主反应。已经从克隆性NK细胞淋巴瘤患者中建立了细胞毒性细胞系。这些细胞可以在白细胞介素-2存在的情况下在培养物中扩增。不过,除了NK-92细胞系外,其他六种已知的NK细胞系均未始终如一地、可重复地表现出高抗肿瘤细胞毒性。只有NK-92细胞能够容易地进行基因操作,以识别特定肿瘤抗原或通过抗体依赖性细胞毒性增强单克隆抗体活性。NK-92也是唯一一种已被输注到晚期癌症患者体内且具有临床益处和最小副作用的细胞系产品。