Robo1 CAR-NK92 and radiotherapy exert synergistic efficacy in solid tumors
Abstract Background The efficacy of chimeric antigen receptor natural killer (CAR-NK) cells in treating solid tumors is often limited, primarily due to the tumor microenvironment (TME), which hinders the recognition and infiltration of CAR-NK cells. Radiotherapy has been shown to modify the TME, enh...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-025-06753-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849334540815826944 |
|---|---|
| author | Mengdi Wu Jie He Jiaxiao Geng Zhiming Wei Rong Cheng Huashun Li Ligang Xing |
| author_facet | Mengdi Wu Jie He Jiaxiao Geng Zhiming Wei Rong Cheng Huashun Li Ligang Xing |
| author_sort | Mengdi Wu |
| collection | DOAJ |
| description | Abstract Background The efficacy of chimeric antigen receptor natural killer (CAR-NK) cells in treating solid tumors is often limited, primarily due to the tumor microenvironment (TME), which hinders the recognition and infiltration of CAR-NK cells. Radiotherapy has been shown to modify the TME, enhance immune cell infiltration, and improve the recognition of tumor cells by immune cells. This study aimed to investigate the effects of combining radiotherapy with CAR-NK cells in a solid tumor model. Methods The Robo1 CAR-NK92 cell line was developed to specifically target Robo1. Tumor cell lines were generated following radiotherapy, and the cytotoxicity and infiltration of Robo1 CAR-NK92 cells in solid tumor models were evaluated both in vitro and in vivo post-radiotherapy. Results The cytotoxicity of Robo1 CAR-NK92 cells against tumor cells was significantly enhanced following radiotherapy, likely due to the upregulation of NKG2D ligands on the surface of the tumor cells. Furthermore, tumor cells post-radiotherapy were found to promote the migration of Robo1 CAR-NK92 cells. In in vivo experiments, the combination of radiotherapy and Robo1 CAR-NK92 cells resulted in prolonged survival and improved tumor control in a solid tumor mouse model. Conclusion Our results indicate that the combination of Robo1 CAR-NK92 therapy and radiotherapy may present a promising approach for the treatment of solid tumors. |
| format | Article |
| id | doaj-art-71093ff4b67240908164e26b0aab7cf3 |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-71093ff4b67240908164e26b0aab7cf32025-08-20T03:45:32ZengBMCJournal of Translational Medicine1479-58762025-07-0123111810.1186/s12967-025-06753-3Robo1 CAR-NK92 and radiotherapy exert synergistic efficacy in solid tumorsMengdi Wu0Jie He1Jiaxiao Geng2Zhiming Wei3Rong Cheng4Huashun Li5Ligang Xing6Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesDepartment of Oncology, The First People’s Hospital of YibinShandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesAsclepius (Soochow) Technology Company GroupAsclepius (Soochow) Technology Company GroupAsclepius (Soochow) Technology Company GroupDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesAbstract Background The efficacy of chimeric antigen receptor natural killer (CAR-NK) cells in treating solid tumors is often limited, primarily due to the tumor microenvironment (TME), which hinders the recognition and infiltration of CAR-NK cells. Radiotherapy has been shown to modify the TME, enhance immune cell infiltration, and improve the recognition of tumor cells by immune cells. This study aimed to investigate the effects of combining radiotherapy with CAR-NK cells in a solid tumor model. Methods The Robo1 CAR-NK92 cell line was developed to specifically target Robo1. Tumor cell lines were generated following radiotherapy, and the cytotoxicity and infiltration of Robo1 CAR-NK92 cells in solid tumor models were evaluated both in vitro and in vivo post-radiotherapy. Results The cytotoxicity of Robo1 CAR-NK92 cells against tumor cells was significantly enhanced following radiotherapy, likely due to the upregulation of NKG2D ligands on the surface of the tumor cells. Furthermore, tumor cells post-radiotherapy were found to promote the migration of Robo1 CAR-NK92 cells. In in vivo experiments, the combination of radiotherapy and Robo1 CAR-NK92 cells resulted in prolonged survival and improved tumor control in a solid tumor mouse model. Conclusion Our results indicate that the combination of Robo1 CAR-NK92 therapy and radiotherapy may present a promising approach for the treatment of solid tumors.https://doi.org/10.1186/s12967-025-06753-3Robo1Chimeric antigen receptorNatural killer cellsRadiation therapySolid tumorsTumor microenvironment |
| spellingShingle | Mengdi Wu Jie He Jiaxiao Geng Zhiming Wei Rong Cheng Huashun Li Ligang Xing Robo1 CAR-NK92 and radiotherapy exert synergistic efficacy in solid tumors Journal of Translational Medicine Robo1 Chimeric antigen receptor Natural killer cells Radiation therapy Solid tumors Tumor microenvironment |
| title | Robo1 CAR-NK92 and radiotherapy exert synergistic efficacy in solid tumors |
| title_full | Robo1 CAR-NK92 and radiotherapy exert synergistic efficacy in solid tumors |
| title_fullStr | Robo1 CAR-NK92 and radiotherapy exert synergistic efficacy in solid tumors |
| title_full_unstemmed | Robo1 CAR-NK92 and radiotherapy exert synergistic efficacy in solid tumors |
| title_short | Robo1 CAR-NK92 and radiotherapy exert synergistic efficacy in solid tumors |
| title_sort | robo1 car nk92 and radiotherapy exert synergistic efficacy in solid tumors |
| topic | Robo1 Chimeric antigen receptor Natural killer cells Radiation therapy Solid tumors Tumor microenvironment |
| url | https://doi.org/10.1186/s12967-025-06753-3 |
| work_keys_str_mv | AT mengdiwu robo1carnk92andradiotherapyexertsynergisticefficacyinsolidtumors AT jiehe robo1carnk92andradiotherapyexertsynergisticefficacyinsolidtumors AT jiaxiaogeng robo1carnk92andradiotherapyexertsynergisticefficacyinsolidtumors AT zhimingwei robo1carnk92andradiotherapyexertsynergisticefficacyinsolidtumors AT rongcheng robo1carnk92andradiotherapyexertsynergisticefficacyinsolidtumors AT huashunli robo1carnk92andradiotherapyexertsynergisticefficacyinsolidtumors AT ligangxing robo1carnk92andradiotherapyexertsynergisticefficacyinsolidtumors |