Yamaguchi Yoshiyuki, Katata Yousuke, Sano Fuminori, Tanioka Hiroaki, Okawaki Makoto, Yamamura Masahiro, Nagasaka Takeshi
Department of Clinical Oncology, Kawasaki Medical School and Hospital, Kurashiki, Okayama 701-0192, Japan.
Mol Clin Oncol. 2020 Nov;13(5):55. doi: 10.3892/mco.2020.2125. Epub 2020 Aug 24.
For several years, adoptive immunotherapy (AIT) has been performed using autologous zoledronate-activated killer (ZAK) cells to develop a novel modality for cancer treatment. In the current study, data from 50 patients with incurable gastric cancer were analyzed. Patients were treated with AIT using intravenous ZAK cells every 3-4 weeks in combination with chemotherapy of the physician's choice. The possible clinical benefits were subsequently examined. The median overall survival (OS) time of all patients was 7.5 months. In patients that received 5 or more rounds of treatment, the OS was 13.5 months. Additionally, the OS times of 1st, 2nd or later line chemotherapy with ZAK cell AIT were 27.3 months and 13.3 months, respectively. No objective response was observed and the disease control rate was 67.9%. No severe adverse event was recorded. Functional Assessment of Cancer Therapy-Biologic Response Modifier analysis revealed possible improvement of quality of life after ZAK cell AIT. Univariate analysis revealed a significant positive association between longer survival times and baseline lymphocyte percentages in white blood cell counts (P<0.001), serum albumin (P=0.001), C-reactive protein (P=0.006), carbohydrate antigen (CA)19-9 (P=0.010), neutrophil-lymphocyte ratio (P<0.001) and Glasgow prognostic score (GPS). Only the GPS value (P=0.024) was a significant survival marker when analyzed using the multivariate Cox proportional hazards model. Although the results cannot provide a definitive conclusion, the current suggested that ZAK cell AIT in combination with chemotherapy is safe, feasible and may be a promising treatment option for patients with incurable gastric cancer. The GPS value at baseline may be a potential biomarker for chemo-immunotherapy.
数年来，一直采用自体唑来膦酸激活的杀伤（ZAK）细胞进行过继性免疫治疗（AIT），以开发一种新型癌症治疗方法。在本研究中，分析了50例无法治愈的胃癌患者的数据。患者接受AIT治疗，每3 - 4周静脉注射ZAK细胞，并结合医生选择的化疗方案。随后检查了可能的临床获益。所有患者的中位总生存期（OS）为7.5个月。接受5轮或更多轮治疗的患者，OS为13.5个月。此外，ZAK细胞AIT联合一线、二线或后续化疗的OS时间分别为27.3个月和13.3个月。未观察到客观缓解，疾病控制率为67.9%。未记录到严重不良事件。癌症治疗功能评估 - 生物反应调节剂分析显示，ZAK细胞AIT后生活质量可能得到改善。单因素分析显示，较长生存期与白细胞计数中的基线淋巴细胞百分比（P<0.001）、血清白蛋白（P = 0.001）、C反应蛋白（P = 0.006）、糖类抗原（CA）19 - 9（P = 0.010）、中性粒细胞与淋巴细胞比值（P<0.001）和格拉斯哥预后评分（GPS）之间存在显著正相关。使用多变量Cox比例风险模型分析时，只有GPS值（P = 0.024）是一个显著的生存标志物。尽管结果不能提供确定性结论，但目前表明ZAK细胞AIT联合化疗是安全、可行的，可能是无法治愈的胃癌患者的一种有前景的治疗选择。基线时的GPS值可能是化学免疫治疗的潜在生物标志物。
