Tonn T, Becker S, Esser R, Schwabe D, Seifried E
Institute for Immunhematology and Transfusionmedicine, Red Cross Blood Donor Service Hessia, Frankfurt/Main, Germany.
J Hematother Stem Cell Res. 2001 Aug;10(4):535-44. doi: 10.1089/15258160152509145.
For years activated natural killer (A-NK) cells have been explored with respect to their efficacy in anticancer therapy, but, except for some anectdotal reports, no clear clinical benefit has been shown. However, as the understanding about the interactions of NK cells and tumor cells advances, the use of A-NK cells might be revisited with more sophisticated approaches that pay tribute to mechanisms which allow tumor cells to escape immune surveillance. Here the highly cytotoxic NK cell line NK-92 seems to be an attractive alternative for use in adoptive immunotherapy, because it was shown to exhibit substantial antitumor activity against a wide range of malignancies in vitro as well as in xenografted SCID mice. NK-92 cells are characterized by an almost complete lack of killer cell immunglobulin-like receptors (KIRs) yet conserved ability to perforin and granzyme B-mediated cytolytic activity, which make them unique among the few established NK and T cell-like cell lines. NK-92 is the only natural killer cell line that has entered clinical trials. Here we discuss the current status of development of this cell line for adoptive immunotherapy (AIT) of malignancies and review our first clinical experience in patients with advanced cancer who have received repeated transfusions of irradiated NK-92 in a phase I/II trial. Also we discuss issues that address safety aspects of immunotherapy with clonal cell lines and describe further manipulations, which hold the potential of significantly improving the clinical outcome of AIT with NK-92.
多年来，人们一直在探索活化自然杀伤（A-NK）细胞在抗癌治疗中的疗效，但除了一些轶事报道外，尚未显示出明显的临床益处。然而，随着对NK细胞与肿瘤细胞相互作用的认识不断深入，可能会用更复杂的方法重新审视A-NK细胞的使用，这些方法考虑到了肿瘤细胞逃避免疫监视的机制。在这里，高细胞毒性的NK细胞系NK-92似乎是过继性免疫治疗中一种有吸引力的选择，因为它在体外以及异种移植的SCID小鼠中均显示出对多种恶性肿瘤具有显著的抗肿瘤活性。NK-92细胞的特征是几乎完全缺乏杀伤细胞免疫球蛋白样受体（KIR），但穿孔素和颗粒酶B介导的细胞溶解活性得以保留，这使其在少数已建立的NK和T细胞样细胞系中独树一帜。NK-92是唯一进入临床试验的自然杀伤细胞系。在此，我们讨论该细胞系用于恶性肿瘤过继性免疫治疗（AIT）的当前发展状况，并回顾我们在I/II期试验中对晚期癌症患者反复输注辐照过的NK-92的首次临床经验。我们还讨论了克隆细胞系免疫治疗安全性方面的问题，并描述了进一步的操作，这些操作有可能显著改善NK-92介导的AIT的临床结果。
