Synergistic Effects of Cabozantinib and EGFR-Specific CAR-NK-92 Cells in Renal Cell Carcinoma
The chimeric antigen receptor-modified immune effector cell (CAR-T and CAR-NK) therapies are newly developed adoptive treatments of cancers. However, their therapeutic efficacy against solid tumors is limited. Combining CAR-T or CAR-NK cells with chemotherapeutic drugs to treat solid tumor may be a...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2017/6915912 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832552966208356352 |
|---|---|
| author | Qing Zhang Kang Tian Jinjing Xu Haixu Zhang Liantao Li Qiang Fu Dafei Chai Huizhong Li Junnian Zheng |
| author_facet | Qing Zhang Kang Tian Jinjing Xu Haixu Zhang Liantao Li Qiang Fu Dafei Chai Huizhong Li Junnian Zheng |
| author_sort | Qing Zhang |
| collection | DOAJ |
| description | The chimeric antigen receptor-modified immune effector cell (CAR-T and CAR-NK) therapies are newly developed adoptive treatments of cancers. However, their therapeutic efficacy against solid tumors is limited. Combining CAR-T or CAR-NK cells with chemotherapeutic drugs to treat solid tumor may be a promising strategy. We developed an epidermal growth factor- (EGFR-) specific third-generation CAR. NK-92 cells were modified with the CAR by lentivirus infection. The specific killing ability of the CAR-modified NK-92 cells (CAR-NK-92) against renal cell carcinoma (RCC) cell lines was confirmed in vitro. The synergistic effects of cabozantinib and EGFR-specific CAR-NK-92 cells were investigated in vitro and in vivo. Our results showed that the CAR-NK-92 cells lyse RCC cells in an EGFR-specific manner. Treatment with cabozantinib could increase EGFR and decrease PD-L1 membrane surface expression in RCC cells and enhance the killing ability of CAR-NK-92 cells against the RCC cells in vitro. Furthermore, the CAR-NK-92 cells show synergistic therapeutic efficacy with cabozantinib against human RCC xenograft models. Our results provided the basis for combination with chemotherapy as a novel strategy for enhancing the therapeutic efficacy of CAR-modified immune effector cells for solid tumors. |
| format | Article |
| id | doaj-art-18b2f7c32a3f406798981f1c7ab6428d |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-18b2f7c32a3f406798981f1c7ab6428d2025-02-03T05:57:12ZengWileyJournal of Immunology Research2314-88612314-71562017-01-01201710.1155/2017/69159126915912Synergistic Effects of Cabozantinib and EGFR-Specific CAR-NK-92 Cells in Renal Cell CarcinomaQing Zhang0Kang Tian1Jinjing Xu2Haixu Zhang3Liantao Li4Qiang Fu5Dafei Chai6Huizhong Li7Junnian Zheng8Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, ChinaCancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, ChinaCancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, ChinaCancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, ChinaCancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, ChinaDepartment of Immunology, Binzhou Medical University, Yantai, Shandong 264003, ChinaCancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, ChinaCancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, ChinaCancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, ChinaThe chimeric antigen receptor-modified immune effector cell (CAR-T and CAR-NK) therapies are newly developed adoptive treatments of cancers. However, their therapeutic efficacy against solid tumors is limited. Combining CAR-T or CAR-NK cells with chemotherapeutic drugs to treat solid tumor may be a promising strategy. We developed an epidermal growth factor- (EGFR-) specific third-generation CAR. NK-92 cells were modified with the CAR by lentivirus infection. The specific killing ability of the CAR-modified NK-92 cells (CAR-NK-92) against renal cell carcinoma (RCC) cell lines was confirmed in vitro. The synergistic effects of cabozantinib and EGFR-specific CAR-NK-92 cells were investigated in vitro and in vivo. Our results showed that the CAR-NK-92 cells lyse RCC cells in an EGFR-specific manner. Treatment with cabozantinib could increase EGFR and decrease PD-L1 membrane surface expression in RCC cells and enhance the killing ability of CAR-NK-92 cells against the RCC cells in vitro. Furthermore, the CAR-NK-92 cells show synergistic therapeutic efficacy with cabozantinib against human RCC xenograft models. Our results provided the basis for combination with chemotherapy as a novel strategy for enhancing the therapeutic efficacy of CAR-modified immune effector cells for solid tumors.http://dx.doi.org/10.1155/2017/6915912 |
| spellingShingle | Qing Zhang Kang Tian Jinjing Xu Haixu Zhang Liantao Li Qiang Fu Dafei Chai Huizhong Li Junnian Zheng Synergistic Effects of Cabozantinib and EGFR-Specific CAR-NK-92 Cells in Renal Cell Carcinoma Journal of Immunology Research |
| title | Synergistic Effects of Cabozantinib and EGFR-Specific CAR-NK-92 Cells in Renal Cell Carcinoma |
| title_full | Synergistic Effects of Cabozantinib and EGFR-Specific CAR-NK-92 Cells in Renal Cell Carcinoma |
| title_fullStr | Synergistic Effects of Cabozantinib and EGFR-Specific CAR-NK-92 Cells in Renal Cell Carcinoma |
| title_full_unstemmed | Synergistic Effects of Cabozantinib and EGFR-Specific CAR-NK-92 Cells in Renal Cell Carcinoma |
| title_short | Synergistic Effects of Cabozantinib and EGFR-Specific CAR-NK-92 Cells in Renal Cell Carcinoma |
| title_sort | synergistic effects of cabozantinib and egfr specific car nk 92 cells in renal cell carcinoma |
| url | http://dx.doi.org/10.1155/2017/6915912 |
| work_keys_str_mv | AT qingzhang synergisticeffectsofcabozantinibandegfrspecificcarnk92cellsinrenalcellcarcinoma AT kangtian synergisticeffectsofcabozantinibandegfrspecificcarnk92cellsinrenalcellcarcinoma AT jinjingxu synergisticeffectsofcabozantinibandegfrspecificcarnk92cellsinrenalcellcarcinoma AT haixuzhang synergisticeffectsofcabozantinibandegfrspecificcarnk92cellsinrenalcellcarcinoma AT liantaoli synergisticeffectsofcabozantinibandegfrspecificcarnk92cellsinrenalcellcarcinoma AT qiangfu synergisticeffectsofcabozantinibandegfrspecificcarnk92cellsinrenalcellcarcinoma AT dafeichai synergisticeffectsofcabozantinibandegfrspecificcarnk92cellsinrenalcellcarcinoma AT huizhongli synergisticeffectsofcabozantinibandegfrspecificcarnk92cellsinrenalcellcarcinoma AT junnianzheng synergisticeffectsofcabozantinibandegfrspecificcarnk92cellsinrenalcellcarcinoma |