한빛사논문
- 조회360
Myeong Geun Choi1,2, Gun Woo Son3, Mi Young Choi3, Jae Seob Jung4, Jin Kyung Rho5, Wonjun Ji1, Byeong Gon Yoon3, Jong-Min Jo3, Yong Man Kim4, Dae-Hyun Ko6, Jae Cheol Lee7 and Chang-Min Choi1,7
1Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mokdong Hospital, College of Medicine, Ewha Womans University, Seoul, South Korea
3C&SR Inc, Uiwang, South Korea
4NKMAX Co., Ltd, Seongnam, South Korea
5Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
6Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
7Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
MGC and GWS contributed equally.
Correspondence to Professor Chang-Min Choi; Dr Jae Cheol Lee
Abstract
Background: Choosing treatments for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients with osimertinib resistance is challenging. We evaluated the safety and efficacy of SNK01 (autologous natural killer (NK) cells) in combination with cytotoxic chemotherapy and/or cetuximab (an anti-EGFR monoclonal antibody) in treating EGFR-mutated NSCLC in this non-clinical and phase I/IIa clinical trial.
Methods: We developed a cell line-derived xenograft-humanized mouse model with an osimertinib-resistant lung cancer cell line. The mice were divided into four groups based on treatment (no treatment, cetuximab, SNK01, and combination groups) and treated weekly for 5 weeks. In the clinical study, 12 patients with EGFR-mutated NSCLC who failed prior tyrosine kinase inhibitor (TKI) received SNK01 weekly in combination with gemcitabine/carboplatin (n=6) or cetuximab/gemcitabine/carboplatin (n=6) and dose escalation of SNK01 following the "3+3" design.
Results: In the non-clinical study, an increase in NK cells in the blood and enhanced NK cell tumor infiltration were observed in the SNK01 group. The volume of tumor extracted after treatment was the smallest in the combination group. In the clinical study, 12 patients (median age, 60.9 years; all adenocarcinoma cases) received SNK01 weekly for 7-8 weeks (4×109 cells/dose (n=6); 6×109 cells/dose (n=6)). The maximum feasible dose of SNK01 was 6×109 cells/dose without dose-limiting toxicity. Efficacy outcomes showed an objective response rate of 25%, disease control rate of 100%, and median progression-free survival of 143 days.
Conclusion: SNK01 in combination with cytotoxic chemotherapy, including cetuximab, for EGFR-mutated NSCLC with TKI resistance was safe and exerted a potential antitumor effect.
논문정보
- Research article
- 2024년 03월 (BRIC 등록일 2024-03-29)
- 국내 연구진
- 의약학 > 종양의학
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