PMID- 34332557 OWN - NLM STAT- MEDLINE DCOM- 20211018 LR - 20211018 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 21 IP - 1 DP - 2021 Jul 31 TI - A phase I/II clinical trial on the efficacy and safety of NKT cells combined with gefitinib for advanced EGFR-mutated non-small-cell lung cancer. PG - 877 LID - 10.1186/s12885-021-08590-1 [doi] LID - 877 AB - BACKGROUND: 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. METHODS: 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. DISCUSSION: 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. TRIAL REGISTRATION: 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 . CI - (c) 2021. The Author(s). FAU - Yu, Wanjun AU - Yu W AD - Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, China. FAU - Ye, Fei AU - Ye F AD - Department of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Yuan, Xiao AU - Yuan X AD - Department of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Ma, Yali AU - Ma Y AD - Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, China. FAU - Mao, Chaoming AU - Mao C AD - Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Li, Xiaoqin AU - Li X AD - Department of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Li, Jian AU - Li J AD - Department of Respiratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Dai, Chunhua AU - Dai C AD - Department of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Qian, Fenhong AU - Qian F AD - Department of Respiratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Li, Junrong AU - Li J AD - Department of Epidemiology and Biostatistics, School of Medicine, Jiangsu University, Zhenjiang, China. FAU - Fan, Xiujuan AU - Fan X AD - Department of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Zhou, Yuepeng AU - Zhou Y AD - Department of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Wang, Deqiang AU - Wang D AD - Department of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Guo, Zhenhong AU - Guo Z AD - National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China. FAU - An, Huazhang AU - An H AD - Shandong Provincial Qianfoshan Hospital, Shandong First Medical University, Jinan, Shandong, China. FAU - Zhang, Minghui AU - Zhang M AD - School of Medicine, Tsinghua University, Beijing, China. immunolzhang@aliyun.com. FAU - Chen, Deyu AU - Chen D AD - Department of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China. cdeyu@hotmail.com. FAU - Xia, Sheng AU - Xia S AUID- ORCID: 0000-0002-0663-6988 AD - Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, China. xiasheng1519@163.com. LA - eng GR - BE2017696/Science and Technology Support Program of Jiangsu Province/ PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial DEP - 20210731 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (B7-H1 Antigen) RN - 0 (CD274 protein, human) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - S65743JHBS (Gefitinib) SB - IM MH - *Adoptive Transfer/adverse effects/methods MH - B7-H1 Antigen/antagonists & inhibitors MH - Carcinoma, Non-Small-Cell Lung/diagnosis/etiology/*therapy MH - Combined Modality Therapy MH - ErbB Receptors/antagonists & inhibitors/genetics MH - Gefitinib/administration & dosage/adverse effects/*therapeutic use MH - Humans MH - Lung Neoplasms/diagnosis/etiology/*therapy MH - Molecular Targeted Therapy MH - *Mutation MH - Natural Killer T-Cells/*immunology/metabolism MH - Treatment Outcome PMC - PMC8325186 OTO - NOTNLM OT - Gefitinib OT - Immunotherapy OT - Natural killer T cell OT - Non-small-cell lung cancer OT - Randomized controlled trial COIS- The authors declare that they have no competing interest. EDAT- 2021/08/02 06:00 MHDA- 2021/10/21 06:00 PMCR- 2021/07/31 CRDT- 2021/08/01 20:25 PHST- 2021/01/26 00:00 [received] PHST- 2021/07/05 00:00 [accepted] PHST- 2021/08/01 20:25 [entrez] PHST- 2021/08/02 06:00 [pubmed] PHST- 2021/10/21 06:00 [medline] PHST- 2021/07/31 00:00 [pmc-release] AID - 10.1186/s12885-021-08590-1 [pii] AID - 8590 [pii] AID - 10.1186/s12885-021-08590-1 [doi] PST - epublish SO - BMC Cancer. 2021 Jul 31;21(1):877. doi: 10.1186/s12885-021-08590-1.