Updated overall survival data and predictive biomarkers of autologous NK cells plus Sintilimab as second-line treatment for advanced non-small cell lung cancer
PurposeCombination strategies involving immune checkpoint inhibitors (ICIs) have been a prominent focus of research in the treatment of non-small cell lung cancer (NSCLC). Our prior findings demonstrated that the combination of autologous NK cells with the PD-1 antibody (Sintilimab), offered promisi...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1595382/full |
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| author | Lin Jia Naifei Chen Xiao Chen Chao Niu Ziling Liu Kewei Ma Lei Yang Yuguang Zhao Wei Song Jin Lu Chen Chen Xiaofeng Cong Xu Wang Yinghui Xu Guozhen Cui Zengguang Liu Rongrong Chen Huan Yin Na Zhang Jiuwei Cui |
| author_facet | Lin Jia Naifei Chen Xiao Chen Chao Niu Ziling Liu Kewei Ma Lei Yang Yuguang Zhao Wei Song Jin Lu Chen Chen Xiaofeng Cong Xu Wang Yinghui Xu Guozhen Cui Zengguang Liu Rongrong Chen Huan Yin Na Zhang Jiuwei Cui |
| author_sort | Lin Jia |
| collection | DOAJ |
| description | PurposeCombination strategies involving immune checkpoint inhibitors (ICIs) have been a prominent focus of research in the treatment of non-small cell lung cancer (NSCLC). Our prior findings demonstrated that the combination of autologous NK cells with the PD-1 antibody (Sintilimab), offered promising efficacy in NSCLC patients who failed the first-line platinum-based chemotherapy. Here, we present updated overall survival (OS) data from the final analysis, aiming to identify patient subgroups that derive maximal benefit from this therapeutic approach.MethodsTwenty NSCLC patients without driver gene mutations were enrolled and treated with a combination of autologous NK cells and Sintilimab every three weeks. Multicolor immunofluorescence staining was applied to evaluate static markers within the tumor microenvironment. Concurrently, dynamic assessments were conducted using next-generation sequencing and monitoring of PD-1/PD-L1 expression on NK cells to identify patient populations with favorable prognoses.ResultsThe median OS was 27.3 months (95% CI, 0.76 to 53.8), with six patients still alive at the follow-up cutoff. A significant correlation was observed between the CD56+PD-L1+ cellular phenotype and extended survival. Clearance of circulating tumor DNA (ctDNA) and an increased percentage of PD-L1+ NK cells following treatment was associated with significantly better survival outcomes. Notably, prolonged treatment exposure did not lead to increased toxicity.ConclusionThe combination of autologous NK cells with Sintilimab significantly enhances long-term survival in NSCLC patients without exacerbating adverse effects, presenting a promising strategy for future combination immunotherapy approaches in NSCLC treatment.Clinical trial registrationhttps://www.clinicaltrials.gov/ct2/show/NCT03958097, identifier NCT03958097. |
| format | Article |
| id | doaj-art-b51d1d3ea3134f42b0243f1c3a65128a |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-b51d1d3ea3134f42b0243f1c3a65128a2025-08-20T03:08:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15953821595382Updated overall survival data and predictive biomarkers of autologous NK cells plus Sintilimab as second-line treatment for advanced non-small cell lung cancerLin Jia0Naifei Chen1Xiao Chen2Chao Niu3Ziling Liu4Kewei Ma5Lei Yang6Yuguang Zhao7Wei Song8Jin Lu9Chen Chen10Xiaofeng Cong11Xu Wang12Yinghui Xu13Guozhen Cui14Zengguang Liu15Rongrong Chen16Huan Yin17Na Zhang18Jiuwei Cui19Cancer center, The First Hospital of Jilin University, Changchun, ChinaCancer center, The First Hospital of Jilin University, Changchun, ChinaCancer center, The First Hospital of Jilin University, Changchun, ChinaCancer center, The First Hospital of Jilin University, Changchun, ChinaCancer center, The First Hospital of Jilin University, Changchun, ChinaCancer center, The First Hospital of Jilin University, Changchun, ChinaCancer center, The First Hospital of Jilin University, Changchun, ChinaCancer center, The First Hospital of Jilin University, Changchun, ChinaCancer center, The First Hospital of Jilin University, Changchun, ChinaCancer center, The First Hospital of Jilin University, Changchun, ChinaCancer center, The First Hospital of Jilin University, Changchun, ChinaCancer center, The First Hospital of Jilin University, Changchun, ChinaCancer center, The First Hospital of Jilin University, Changchun, ChinaCancer center, The First Hospital of Jilin University, Changchun, ChinaCancer center, The First Hospital of Jilin University, Changchun, ChinaCancer center, The First Hospital of Jilin University, Changchun, ChinaDepartment of Medical Center, Geneplus-Beijing Institute, Beijing, ChinaDepartment of Medical Center, Geneplus-Beijing Institute, Beijing, ChinaDepartment of Medical Affairs, Genecast Biotechnology, Wuxi, ChinaCancer center, The First Hospital of Jilin University, Changchun, ChinaPurposeCombination strategies involving immune checkpoint inhibitors (ICIs) have been a prominent focus of research in the treatment of non-small cell lung cancer (NSCLC). Our prior findings demonstrated that the combination of autologous NK cells with the PD-1 antibody (Sintilimab), offered promising efficacy in NSCLC patients who failed the first-line platinum-based chemotherapy. Here, we present updated overall survival (OS) data from the final analysis, aiming to identify patient subgroups that derive maximal benefit from this therapeutic approach.MethodsTwenty NSCLC patients without driver gene mutations were enrolled and treated with a combination of autologous NK cells and Sintilimab every three weeks. Multicolor immunofluorescence staining was applied to evaluate static markers within the tumor microenvironment. Concurrently, dynamic assessments were conducted using next-generation sequencing and monitoring of PD-1/PD-L1 expression on NK cells to identify patient populations with favorable prognoses.ResultsThe median OS was 27.3 months (95% CI, 0.76 to 53.8), with six patients still alive at the follow-up cutoff. A significant correlation was observed between the CD56+PD-L1+ cellular phenotype and extended survival. Clearance of circulating tumor DNA (ctDNA) and an increased percentage of PD-L1+ NK cells following treatment was associated with significantly better survival outcomes. Notably, prolonged treatment exposure did not lead to increased toxicity.ConclusionThe combination of autologous NK cells with Sintilimab significantly enhances long-term survival in NSCLC patients without exacerbating adverse effects, presenting a promising strategy for future combination immunotherapy approaches in NSCLC treatment.Clinical trial registrationhttps://www.clinicaltrials.gov/ct2/show/NCT03958097, identifier NCT03958097.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1595382/fullnon-small cell lung cancersecond line therapyautologous NK cellssintilimabimmunotherapy |
| spellingShingle | Lin Jia Naifei Chen Xiao Chen Chao Niu Ziling Liu Kewei Ma Lei Yang Yuguang Zhao Wei Song Jin Lu Chen Chen Xiaofeng Cong Xu Wang Yinghui Xu Guozhen Cui Zengguang Liu Rongrong Chen Huan Yin Na Zhang Jiuwei Cui Updated overall survival data and predictive biomarkers of autologous NK cells plus Sintilimab as second-line treatment for advanced non-small cell lung cancer Frontiers in Immunology non-small cell lung cancer second line therapy autologous NK cells sintilimab immunotherapy |
| title | Updated overall survival data and predictive biomarkers of autologous NK cells plus Sintilimab as second-line treatment for advanced non-small cell lung cancer |
| title_full | Updated overall survival data and predictive biomarkers of autologous NK cells plus Sintilimab as second-line treatment for advanced non-small cell lung cancer |
| title_fullStr | Updated overall survival data and predictive biomarkers of autologous NK cells plus Sintilimab as second-line treatment for advanced non-small cell lung cancer |
| title_full_unstemmed | Updated overall survival data and predictive biomarkers of autologous NK cells plus Sintilimab as second-line treatment for advanced non-small cell lung cancer |
| title_short | Updated overall survival data and predictive biomarkers of autologous NK cells plus Sintilimab as second-line treatment for advanced non-small cell lung cancer |
| title_sort | updated overall survival data and predictive biomarkers of autologous nk cells plus sintilimab as second line treatment for advanced non small cell lung cancer |
| topic | non-small cell lung cancer second line therapy autologous NK cells sintilimab immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1595382/full |
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