Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
National Clinical Research Center for Cancer, Tianjin, China.
Thorac Cancer. 2021 Jan;12(2):145-152. doi: 10.1111/1759-7714.13731. Epub 2020 Nov 4.
Programmed death-1 (PD-1) blocking antibodies have been shown to improve progression-free survival (PFS) and overall survival in a subset of patients with non-small cell lung cancer (NSCLC). However, the objective response rate with these agents remains low, and the vast majority of NSCLC patients require alternative combination treatment regimens to prolong their survival. The purpose of this study was to evaluate the clinical efficacy of autologous cytokine-induced killer (CIK) cell infusions combined with PD-1 blocking antibodies in patients with NSCLC.
In this preliminary study, we investigated the safety and immune function effectiveness of PD-1 blockade antibodies pembrolizumab or nivolumab administered in combination with or without autologous CIK cell infusions in 18 patients with advanced NSCLC. The peripheral blood mononuclear cells were isolated from these patients and the expression level of some cell surface molecules like PD-1 were detected using flow cytometry to reflect the effectiveness of this combination regimen.
No treatment-related deaths occurred in either cohort. In comparison with the pretreatment level, CD3 CD56 CD16 T cells were significantly increased with the combination therapy, while myeloid-derived suppressor cells were significantly increased with PD-1 blocking antibody therapy alone but not with combination therapy. Although the serum interleukin-4 level was downregulated following treatment with the combination regimen, interferon-γ levels were unchanged.
The purpose of this clinical study was to report the clinical efficacy and lack of exacerbated autoimmune adverse events with a combination of PD-1 blockade and CIK cell infusions in patients with advanced NSCLC, further supporting assessments of this combination in future clinical trials.
程序性死亡-1(PD-1)阻断抗体已被证明可改善非小细胞肺癌(NSCLC)患者亚组的无进展生存期(PFS)和总生存期。然而,这些药物的客观缓解率仍然较低,绝大多数 NSCLC 患者需要替代联合治疗方案来延长生存时间。本研究旨在评估自体细胞因子诱导的杀伤(CIK)细胞输注联合 PD-1 阻断抗体在 NSCLC 患者中的临床疗效。
在这项初步研究中,我们调查了 PD-1 阻断抗体 pembrolizumab 或 nivolumab 联合或不联合自体 CIK 细胞输注在 18 例晚期 NSCLC 患者中的安全性和免疫功能效果。从这些患者中分离外周血单核细胞,并使用流式细胞术检测某些细胞表面分子(如 PD-1)的表达水平,以反映该联合方案的效果。
两个队列均未发生与治疗相关的死亡事件。与预处理水平相比,CD3 CD56 CD16 T 细胞在联合治疗时显著增加,而髓样来源的抑制细胞在 PD-1 阻断抗体单独治疗时显著增加,但在联合治疗时没有增加。虽然联合治疗后血清白细胞介素-4 水平下调,但干扰素-γ水平不变。
本临床研究的目的是报告 PD-1 阻断和 CIK 细胞输注联合治疗晚期 NSCLC 患者的临床疗效和无加重自身免疫不良事件,进一步支持在未来临床试验中评估该联合方案。