Boyiadzis Michael, Agha Mounzer, Redner Robert L, Sehgal Alison, Im Annie, Hou Jing-Zhou, Farah Rafic, Dorritie Kathleen A, Raptis Anastasios, Lim Seah H, Wang Hong, Lapteva Natalia, Mei Zhuyong, Butterfield Lisa H, Rooney Cliona M, Whiteside Theresa L
University of Pittsburgh, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
University of Pittsburgh, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Cytotherapy. 2017 Oct;19(10):1225-1232. doi: 10.1016/j.jcyt.2017.07.008. Epub 2017 Aug 30.
Activated NK cells (aNK) generated by expansion of a human interleukin-2-dependent NK cell line (NK-92) were shown to mediate strong anti-leukemia activity. This phase 1 study evaluated feasibility, safety, and activity of aNK cells adoptively transferred to patients with refractory/relapsed acute myeloid leukemia (AML). In addition, effects of these aNK cells on the patient's immune system were evaluated.
Two cell-dose levels (1 × 10 cells/m and 3 × 10 cells/m) were used. One treatment course consisted of two infusions of the same cell dose, each cell infusion delivered 24 h apart. The aNK cells were administered in the outpatient setting.
Seven patients with refractory/relapsed AML were treated with a total of 20 aNK cell infusions. None of the 7 patients experienced dose-limiting toxicities during the aNK cell administration or during 21 days of the post-infusion observation period. No grade 3-4 toxicities (probable or definite) related to aNK cell infusions occurred. Activity was transient in 3 of 7 patients. No significant changes in the patient's lymphocyte counts, subsets frequency, phenotype or activity were observed post-infusion. Cell dose-dependent effects in the plasma levels of several cytokines were observed.
The trial demonstrated the safety and feasibility of adoptive cell therapy with "off-the-shelf" aNK cells in patients with refractory/relapsed AML. These data provide the foundation for future combination immunotherapy trials and for the optimization of aNK cell based therapies in patients with AML.
通过扩增人白细胞介素-2依赖的自然杀伤细胞系（NK-92）产生的活化自然杀伤细胞（aNK）已显示出介导强大的抗白血病活性。这项1期研究评估了过继转移至难治性/复发性急性髓系白血病（AML）患者的aNK细胞的可行性、安全性和活性。此外，还评估了这些aNK细胞对患者免疫系统的影响。
使用了两个细胞剂量水平（1×10⁸细胞/m²和3×10⁸细胞/m²）。一个疗程包括两次输注相同剂量的细胞，每次细胞输注间隔24小时。aNK细胞在门诊环境中给药。
7例难治性/复发性AML患者共接受了20次aNK细胞输注。7例患者中无一例在aNK细胞给药期间或输注后21天的观察期内出现剂量限制性毒性。未发生与aNK细胞输注相关的3-4级毒性（可能或确定）。7例患者中有3例活性是短暂的。输注后未观察到患者淋巴细胞计数、亚群频率、表型或活性有显著变化。观察到几种细胞因子血浆水平存在细胞剂量依赖性效应。
该试验证明了用“现成的”aNK细胞对难治性/复发性AML患者进行过继性细胞治疗的安全性和可行性。这些数据为未来的联合免疫治疗试验以及AML患者基于aNK细胞疗法的优化提供了基础。
