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Safety and efficacy of SNK01 (autologous natural killer cells) in combination with cytotoxic chemotherapy and/or cetuximab after failure of prior tyrosine kinase inhibitor in non-small cell lung cancer: non-clinical mouse model and phase I/IIa clinical study

Title
Safety and efficacy of SNK01 (autologous natural killer cells) in combination with cytotoxic chemotherapy and/or cetuximab after failure of prior tyrosine kinase inhibitor in non-small cell lung cancer: non-clinical mouse model and phase I/IIa clinical study
Authors
ChoiMyeong GeunSonGun WooMi YoungJungJae SeobRhoJin KyungJiWonjunYoonByeong GonJoJong-MinKimYong ManKoDae-HyunLeeJae CheolChang-Min
Ewha Authors
최명근
SCOPUS Author ID
최명근scopus
Issue Date
2024
Journal Title
Journal for ImmunoTherapy of Cancer
ISSN
2051-1426JCR Link
Citation
Journal for ImmunoTherapy of Cancer vol. 12, no. 3
Publisher
BMJ Publishing Group
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
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. © Author(s) (or their employer(s)) 2024.
DOI
10.1136/jitc-2023-008585
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의료원 > 의료원 > Journal papers
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