Evaluation of B7-H3 Targeted Immunotherapy in a 3D Organoid Model of Craniopharyngioma
A craniopharyngioma (CP) is a rare epithelial tumor of the sellar and parasellar region. CPs are difficult to treat due to their anatomical proximity to critical nervous structures, which limits the ability of the surgeon to completely resect the lesion, exposing patients to a high risk of recurrenc...
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MDPI AG
2022-11-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/12/1744 |
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| author | Mei Tang Caili Chen Guoqing Wang Yuelong Wang Zongliang Zhang Hexian Li Qizhong Lu Zeng Wang Shasha Zhao Chen Yang Kunhong Zhong Ruyuan Zhang Liping Guo Zhu Yuan Chunlai Nie Aiping Tong |
| author_facet | Mei Tang Caili Chen Guoqing Wang Yuelong Wang Zongliang Zhang Hexian Li Qizhong Lu Zeng Wang Shasha Zhao Chen Yang Kunhong Zhong Ruyuan Zhang Liping Guo Zhu Yuan Chunlai Nie Aiping Tong |
| author_sort | Mei Tang |
| collection | DOAJ |
| description | A craniopharyngioma (CP) is a rare epithelial tumor of the sellar and parasellar region. CPs are difficult to treat due to their anatomical proximity to critical nervous structures, which limits the ability of the surgeon to completely resect the lesion, exposing patients to a high risk of recurrence. The treatment of craniopharyngiomas is primarily surgery and radiotherapy. So far, neither a cell line nor an animal model has been established, and thus data on other treatment options, such as chemotherapy and immunotherapy, are limited. Here, the expression profile of the pan-cancer antigen B7-H3 in various cancer types including CP was examined by immunohistochemistry. An in vitro organoid model was established by using fresh tissue biospecimens of CP. Based on the organoid model, we evaluated the antitumor efficacy of B7-H3-targeted immunotherapy on CP. As a result, the highest expression of B7-H3 was observed in CP tissues across various cancer types. Although B7-H3-targeted chimeric antigen-receptor T cells show obvious tumor-killing effects in the traditional 2D cell culture model, limited antitumor effects were observed in the 3D organoid model. The B7-H3-targeted antibody-DM1 conjugate exhibited a potent tumor suppression function both in 2D and 3D models. In conclusion, for the first time, we established an organoid model for CP and our results support that B7-H3 might serve as a promising target for antibody-drug conjugate therapy against craniopharyngioma. |
| first_indexed | 2024-03-09T17:17:10Z |
| format | Article |
| id | doaj.art-59b47f0e29904f10a29c1c8ef0530947 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T17:17:10Z |
| publishDate | 2022-11-01 |
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| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-59b47f0e29904f10a29c1c8ef05309472023-11-24T13:32:34ZengMDPI AGBiomolecules2218-273X2022-11-011212174410.3390/biom12121744Evaluation of B7-H3 Targeted Immunotherapy in a 3D Organoid Model of CraniopharyngiomaMei Tang0Caili Chen1Guoqing Wang2Yuelong Wang3Zongliang Zhang4Hexian Li5Qizhong Lu6Zeng Wang7Shasha Zhao8Chen Yang9Kunhong Zhong10Ruyuan Zhang11Liping Guo12Zhu Yuan13Chunlai Nie14Aiping Tong15State Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, ChinaDepartment of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, ChinaDepartment of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, ChinaDepartment of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, ChinaState Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, ChinaState Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, ChinaState Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, ChinaState Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, ChinaState Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, ChinaState Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, ChinaState Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, ChinaState Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, ChinaState Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, ChinaState Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, ChinaState Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, ChinaState Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, ChinaA craniopharyngioma (CP) is a rare epithelial tumor of the sellar and parasellar region. CPs are difficult to treat due to their anatomical proximity to critical nervous structures, which limits the ability of the surgeon to completely resect the lesion, exposing patients to a high risk of recurrence. The treatment of craniopharyngiomas is primarily surgery and radiotherapy. So far, neither a cell line nor an animal model has been established, and thus data on other treatment options, such as chemotherapy and immunotherapy, are limited. Here, the expression profile of the pan-cancer antigen B7-H3 in various cancer types including CP was examined by immunohistochemistry. An in vitro organoid model was established by using fresh tissue biospecimens of CP. Based on the organoid model, we evaluated the antitumor efficacy of B7-H3-targeted immunotherapy on CP. As a result, the highest expression of B7-H3 was observed in CP tissues across various cancer types. Although B7-H3-targeted chimeric antigen-receptor T cells show obvious tumor-killing effects in the traditional 2D cell culture model, limited antitumor effects were observed in the 3D organoid model. The B7-H3-targeted antibody-DM1 conjugate exhibited a potent tumor suppression function both in 2D and 3D models. In conclusion, for the first time, we established an organoid model for CP and our results support that B7-H3 might serve as a promising target for antibody-drug conjugate therapy against craniopharyngioma.https://www.mdpi.com/2218-273X/12/12/1744craniopharyngiomaB7-H3organoidimmunotherapybrain cancer |
| spellingShingle | Mei Tang Caili Chen Guoqing Wang Yuelong Wang Zongliang Zhang Hexian Li Qizhong Lu Zeng Wang Shasha Zhao Chen Yang Kunhong Zhong Ruyuan Zhang Liping Guo Zhu Yuan Chunlai Nie Aiping Tong Evaluation of B7-H3 Targeted Immunotherapy in a 3D Organoid Model of Craniopharyngioma Biomolecules craniopharyngioma B7-H3 organoid immunotherapy brain cancer |
| title | Evaluation of B7-H3 Targeted Immunotherapy in a 3D Organoid Model of Craniopharyngioma |
| title_full | Evaluation of B7-H3 Targeted Immunotherapy in a 3D Organoid Model of Craniopharyngioma |
| title_fullStr | Evaluation of B7-H3 Targeted Immunotherapy in a 3D Organoid Model of Craniopharyngioma |
| title_full_unstemmed | Evaluation of B7-H3 Targeted Immunotherapy in a 3D Organoid Model of Craniopharyngioma |
| title_short | Evaluation of B7-H3 Targeted Immunotherapy in a 3D Organoid Model of Craniopharyngioma |
| title_sort | evaluation of b7 h3 targeted immunotherapy in a 3d organoid model of craniopharyngioma |
| topic | craniopharyngioma B7-H3 organoid immunotherapy brain cancer |
| url | https://www.mdpi.com/2218-273X/12/12/1744 |
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