Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, China.
Department of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.
BMC Cancer. 2021 Jul 31;21(1):877. doi: 10.1186/s12885-021-08590-1.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, have achieved good efficacy in EGFR mutation-positive non-small-cell lung cancer (NSCLC) patients, but eventual drug resistance is inevitable. Thus, new TKI-based combination therapies should be urgently explored to extend the overall survival time of these patients. CD8 + CD56+ natural killer T (NKT) cells are a natural and unique subset of lymphocytes in humans that present characteristics of T and NK cells and exert cytotoxicity on tumour cells in a granzyme B-dependent manner. The aim of this trial was to explore the efficacy and safety of CD8 + CD56+ NKT cell immunotherapy combined with gefitinib in patients with advanced EGFR-mutated NSCLC.
The study was designed as a prospective, randomized, controlled, open-label, phase I/II trial that includes 30 patients with EGFR mutation-positive stage III/IV NSCLC. All patients will be randomized in blocks at a 1:1 ratio and treated with gefitinib 250 mg/day monotherapy or combination therapy with allogeneic CD8 + CD56+ NKT cell infusions twice per month for 12 cycles or until disease progression occurs. The effectiveness of this treatment will be evaluated based on by progression-free survival (PFS), the time to progression (TTP), overall response rate (ORR), disease control rate (DCR) and overall survival (OS). The safety of the trail is being assessed based on adverse events (AEs). Recruitment and data collection, which started in December 2017, are ongoing.
Although immunotherapy, including programmed death-1/programmed death-1 ligand (PD-1/PD-L1) immunotherapy, has been used for NSCLC treatment with or without EGFR-TKIs, its clear efficacy still has not been shown. Assessing the safety and therapeutic potential of allogeneic CD8 + CD56+ NKT killer cells in combination with EGFR-TKIs in NSCLC will be of great interest.
This trial (Phase I/II Trails of NKT Cell in Combination With Gefitinib For Non Small Cell Lung Cancer) was registered on 21 November 2017 with www.chictr.org.cn , ChiCTR-IIR-17013471 .
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs），如吉非替尼，在 EGFR 突变阳性非小细胞肺癌（NSCLC）患者中已取得良好疗效，但最终不可避免会产生耐药性。因此，应迫切探索新的基于 TKI 的联合治疗方法，以延长这些患者的总生存时间。CD8+CD56+自然杀伤 T（NKT）细胞是人类中一种天然而独特的淋巴细胞亚群，具有 T 细胞和 NK 细胞的特征，并以颗粒酶 B 依赖的方式对肿瘤细胞发挥细胞毒性作用。本试验旨在探讨 CD8+CD56+NKT 细胞免疫疗法联合吉非替尼治疗晚期 EGFR 突变阳性 NSCLC 的疗效和安全性。
该研究设计为前瞻性、随机、对照、开放标签、I/II 期试验，纳入 30 例 EGFR 突变阳性 III/IV 期 NSCLC 患者。所有患者将按 1:1 比例分组，以吉非替尼 250mg/d 单药治疗或联合每月两次同种异体 CD8+CD56+NKT 细胞输注 12 个周期，直至疾病进展。根据无进展生存期（PFS）、进展时间（TTP）、总缓解率（ORR）、疾病控制率（DCR）和总生存期（OS）评估该治疗的疗效。根据不良事件（AEs）评估试验的安全性。招募和数据收集于 2017 年 12 月开始，正在进行中。
尽管免疫疗法，包括程序性死亡受体 1/程序性死亡受体配体（PD-1/PD-L1）免疫疗法，已用于 EGFR-TKI 治疗或不治疗 NSCLC，但明确疗效尚未显现。评估同种异体 CD8+CD56+NKT 杀伤细胞与 EGFR-TKIs 联合治疗 NSCLC 的安全性和治疗潜力将具有重要意义。
该试验（NKT 细胞联合吉非替尼治疗非小细胞肺癌的 I/II 期试验）于 2017 年 11 月 21 日在中国临床试验注册中心（www.chictr.org.cn，ChiCTR-IIR-17013471）注册。
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