Chiorean E G, Miller J S
Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota Cancer Center, Minneapolis, MN 55455, USA.
J Hematother Stem Cell Res. 2001 Aug;10(4):451-63. doi: 10.1089/15258160152509073.
Natural killer (NK) cells are unique lymphocytes capable of lysing target cells without prior immunization. NK cells activated with cytokines, like interleukin-2 (IL-2), have been used since the 1980s as adoptive immunotherapy against metastatic solid tumors, but their effectiveness has been limited. The mechanisms by which NK cells recognize their targets are complex, including newly identified receptors that recognize class I MHC molecules. Understanding these mechanisms may support the use of NK cells as clinical therapy against infectious diseases and cancer. We have been interested in the use of NK cells clinically for their potential to eradicate minimal residual disease and prevent relapses after autologous stem cell transplantation. Several strategies are discussed to increase the specificity and efficacy of NK cell therapy. One method is to increase the targeting of NK cells by the use of monoclonal antibodies. Another approach uses allogeneic NK cells to overcome the inhibitory receptor mechanisms that may block target cell lysis by recognition of class I molecules. These and other novel strategies may prove to be attractive and effective immunotherapeutic tools to manipulate NK cells to fight human disease.
自然杀伤（NK）细胞是一类独特的淋巴细胞，能够在无需预先免疫的情况下裂解靶细胞。自20世纪80年代以来，用细胞因子（如白细胞介素-2，IL-2）激活的NK细胞就被用作转移性实体瘤的过继性免疫疗法，但其疗效有限。NK细胞识别靶细胞的机制很复杂，包括新发现的识别I类MHC分子的受体。了解这些机制可能有助于将NK细胞用作针对传染病和癌症的临床疗法。我们一直对NK细胞在临床上的应用感兴趣，因为它们有潜力根除微小残留病并预防自体干细胞移植后的复发。本文讨论了几种提高NK细胞疗法特异性和疗效的策略。一种方法是通过使用单克隆抗体来增强NK细胞的靶向性。另一种方法是使用同种异体NK细胞来克服可能因识别I类分子而阻断靶细胞裂解的抑制性受体机制。这些以及其他新策略可能被证明是有吸引力且有效的免疫治疗工具，可用于操控NK细胞来对抗人类疾病。
