A Novel Sushi-IL15-PD1 CAR-NK92 Cell Line With Enhanced and PD-L1 Targeted Cytotoxicity Against Pancreatic Cancer Cells
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and lethal malignancy with a limited response to current therapies. Novel and effective treatment is urgently needed. Herein, a chimeric antigen receptor (CAR)-NK92 cell line, with an interleukin (IL)-15Rα-sushi/IL-15 complex and a Progr...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.726985/full |
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| author | Da-Lai Xu Da-Lai Xu Da-Lai Xu Yuan-Qing He Bin Xiao Bin Xiao Yuan Si Jian Shi Jian Shi Jian Shi Xue-Ang Liu Xue-Ang Liu Xue-Ang Liu Lei Tian Lei Tian Qian Ren Ya-Song Wu Yi Zhu Yi Zhu Yi Zhu |
| author_facet | Da-Lai Xu Da-Lai Xu Da-Lai Xu Yuan-Qing He Bin Xiao Bin Xiao Yuan Si Jian Shi Jian Shi Jian Shi Xue-Ang Liu Xue-Ang Liu Xue-Ang Liu Lei Tian Lei Tian Qian Ren Ya-Song Wu Yi Zhu Yi Zhu Yi Zhu |
| author_sort | Da-Lai Xu |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and lethal malignancy with a limited response to current therapies. Novel and effective treatment is urgently needed. Herein, a chimeric antigen receptor (CAR)-NK92 cell line, with an interleukin (IL)-15Rα-sushi/IL-15 complex and a Programmed cell death-1(PD1) signal inverter was constructed and named SP (Sushi-IL15-PD1). We showed that CAR expression enabled SP cells to proliferate independently of IL-2 and became more resistant to nutrition starvation-induced apoptosis. Meanwhile, SP cells were more effective than NK92 in PDAC cell killing assays in vitro and in vivo, and there was a positive correlation between the killing capability of SP cells and PD-L1 expression in pancreatic cancer cells. Based on the synergistic and comprehensive effects of the special CAR structure, the adhesion, responsiveness, degranulation efficiency, targeted delivery of cytotoxic granule content, and cytotoxicity of SP cells were significantly stronger than those of NK92. In conclusion, the SP cell line is a promising adoptive immunotherapy cell line and has potential value as an adjuvant treatment for pancreatic cancer, especially in patients with high PD-L1 expression. |
| first_indexed | 2024-12-13T19:24:36Z |
| format | Article |
| id | doaj.art-cbe632a0437042ccb86f744d264749fd |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-13T19:24:36Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-cbe632a0437042ccb86f744d264749fd2022-12-21T23:34:04ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-03-011210.3389/fonc.2022.726985726985A Novel Sushi-IL15-PD1 CAR-NK92 Cell Line With Enhanced and PD-L1 Targeted Cytotoxicity Against Pancreatic Cancer CellsDa-Lai Xu0Da-Lai Xu1Da-Lai Xu2Yuan-Qing He3Bin Xiao4Bin Xiao5Yuan Si6Jian Shi7Jian Shi8Jian Shi9Xue-Ang Liu10Xue-Ang Liu11Xue-Ang Liu12Lei Tian13Lei Tian14Qian Ren15Ya-Song Wu16Yi Zhu17Yi Zhu18Yi Zhu19Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaPancreas Institute of Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaLaboratory Animal Research Center, Jiangsu University, Zhenjiang, ChinaPancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaPancreas Institute of Nanjing Medical University, Nanjing, ChinaResearch & Development Department, Timmune Biotech Inc., Tianjin, ChinaPancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaPancreas Institute of Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaPancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaPancreas Institute of Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaPancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaPancreas Institute of Nanjing Medical University, Nanjing, ChinaLaboratory Animal Research Center, Jiangsu University, Zhenjiang, ChinaResearch & Development Department, Timmune Biotech Inc., Tianjin, ChinaPancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaPancreas Institute of Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and lethal malignancy with a limited response to current therapies. Novel and effective treatment is urgently needed. Herein, a chimeric antigen receptor (CAR)-NK92 cell line, with an interleukin (IL)-15Rα-sushi/IL-15 complex and a Programmed cell death-1(PD1) signal inverter was constructed and named SP (Sushi-IL15-PD1). We showed that CAR expression enabled SP cells to proliferate independently of IL-2 and became more resistant to nutrition starvation-induced apoptosis. Meanwhile, SP cells were more effective than NK92 in PDAC cell killing assays in vitro and in vivo, and there was a positive correlation between the killing capability of SP cells and PD-L1 expression in pancreatic cancer cells. Based on the synergistic and comprehensive effects of the special CAR structure, the adhesion, responsiveness, degranulation efficiency, targeted delivery of cytotoxic granule content, and cytotoxicity of SP cells were significantly stronger than those of NK92. In conclusion, the SP cell line is a promising adoptive immunotherapy cell line and has potential value as an adjuvant treatment for pancreatic cancer, especially in patients with high PD-L1 expression.https://www.frontiersin.org/articles/10.3389/fonc.2022.726985/fullpancreatic ductal adenocarcinomaChimeric antigen receptor (CAR)IL-15IL-15Rα-sushiprogrammed cell death ligand 1 (PD-L1)adoptive immunotherapy |
| spellingShingle | Da-Lai Xu Da-Lai Xu Da-Lai Xu Yuan-Qing He Bin Xiao Bin Xiao Yuan Si Jian Shi Jian Shi Jian Shi Xue-Ang Liu Xue-Ang Liu Xue-Ang Liu Lei Tian Lei Tian Qian Ren Ya-Song Wu Yi Zhu Yi Zhu Yi Zhu A Novel Sushi-IL15-PD1 CAR-NK92 Cell Line With Enhanced and PD-L1 Targeted Cytotoxicity Against Pancreatic Cancer Cells Frontiers in Oncology pancreatic ductal adenocarcinoma Chimeric antigen receptor (CAR) IL-15 IL-15Rα-sushi programmed cell death ligand 1 (PD-L1) adoptive immunotherapy |
| title | A Novel Sushi-IL15-PD1 CAR-NK92 Cell Line With Enhanced and PD-L1 Targeted Cytotoxicity Against Pancreatic Cancer Cells |
| title_full | A Novel Sushi-IL15-PD1 CAR-NK92 Cell Line With Enhanced and PD-L1 Targeted Cytotoxicity Against Pancreatic Cancer Cells |
| title_fullStr | A Novel Sushi-IL15-PD1 CAR-NK92 Cell Line With Enhanced and PD-L1 Targeted Cytotoxicity Against Pancreatic Cancer Cells |
| title_full_unstemmed | A Novel Sushi-IL15-PD1 CAR-NK92 Cell Line With Enhanced and PD-L1 Targeted Cytotoxicity Against Pancreatic Cancer Cells |
| title_short | A Novel Sushi-IL15-PD1 CAR-NK92 Cell Line With Enhanced and PD-L1 Targeted Cytotoxicity Against Pancreatic Cancer Cells |
| title_sort | novel sushi il15 pd1 car nk92 cell line with enhanced and pd l1 targeted cytotoxicity against pancreatic cancer cells |
| topic | pancreatic ductal adenocarcinoma Chimeric antigen receptor (CAR) IL-15 IL-15Rα-sushi programmed cell death ligand 1 (PD-L1) adoptive immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.726985/full |
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