{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:09:52Z","timestamp":1790222992075,"version":"4.1.0"},"reference-count":28,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T00:00:00Z","timestamp":1669248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073404"],"award-info":[{"award-number":["82073404"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021-I2M-5-075"],"award-info":[{"award-number":["2021-I2M-5-075"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2019RU067"],"award-info":[{"award-number":["2019RU067"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CAMS Innovation Fund for Medical Science (CIFMS)","award":["82073404"],"award-info":[{"award-number":["82073404"]}]},{"name":"CAMS Innovation Fund for Medical Science (CIFMS)","award":["2021-I2M-5-075"],"award-info":[{"award-number":["2021-I2M-5-075"]}]},{"name":"CAMS Innovation Fund for Medical Science (CIFMS)","award":["2019RU067"],"award-info":[{"award-number":["2019RU067"]}]},{"name":"Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences","award":["82073404"],"award-info":[{"award-number":["82073404"]}]},{"name":"Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences","award":["2021-I2M-5-075"],"award-info":[{"award-number":["2021-I2M-5-075"]}]},{"name":"Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences","award":["2019RU067"],"award-info":[{"award-number":["2019RU067"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/biom12121744","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T01:46:56Z","timestamp":1669254416000},"page":"1744","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Evaluation of B7-H3 Targeted Immunotherapy in a 3D Organoid Model of Craniopharyngioma"],"prefix":"10.3390","volume":"12","author":[{"given":"Mei","family":"Tang","sequence":"first","affiliation":[{"name":"State 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caili","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuelong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"State 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hexian","family":"Li","sequence":"additional","affiliation":[{"name":"State 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qizhong","family":"Lu","sequence":"additional","affiliation":[{"name":"State 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeng","family":"Wang","sequence":"additional","affiliation":[{"name":"State 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Zhao","sequence":"additional","affiliation":[{"name":"State 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"State 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunhong","family":"Zhong","sequence":"additional","affiliation":[{"name":"State 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Guo","sequence":"additional","affiliation":[{"name":"State 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Yuan","sequence":"additional","affiliation":[{"name":"State 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlai","family":"Nie","sequence":"additional","affiliation":[{"name":"State 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Tong","sequence":"additional","affiliation":[{"name":"State 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/s41572-019-0125-9","article-title":"Craniopharyngioma","volume":"5","author":"Merchant","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/nrendo.2013.125","article-title":"Paediatrics: Surgical strategy and quality of life in craniopharyngioma","volume":"9","year":"2013","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/nrendo.2010.168","article-title":"Childhood craniopharyngioma\u2013current concepts in diagnosis, therapy and follow-up","volume":"6","year":"2010","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/nrendo.2016.217","article-title":"New outlook on the diagnosis, treatment and follow-up of childhood-onset craniopharyngioma","volume":"13","author":"Merchant","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s11102-012-0428-2","article-title":"Mortality and morbidity in adult craniopharyngioma","volume":"16","author":"Erfurth","year":"2012","journal-title":"Pituitary"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1016\/S0002-9440(10)64477-X","article-title":"Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations","volume":"161","author":"Sekine","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/ng.2868","article-title":"Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas","volume":"46","author":"Brastianos","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s11102-018-0890-6","article-title":"Can tissue biomarkers reliably predict the biological behavior of craniopharyngiomas? A comprehensive overview","volume":"21","author":"Prieto","year":"2018","journal-title":"Pituitary"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"E4","DOI":"10.3171\/2016.8.FOCUS16307","article-title":"Molecular pathology of adamantinomatous craniopharyngioma: Review and opportunities for practice","volume":"41","author":"Apps","year":"2016","journal-title":"Neurosurg. Focus"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1007\/s11102-015-0663-4","article-title":"Pronounced response of papillary craniopharyngioma to treatment with vemurafenib, a BRAF inhibitor","volume":"19","author":"Aylwin","year":"2015","journal-title":"Pituitary"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.bbrc.2019.04.142","article-title":"Frequent B7-H3 overexpression in craniopharyngioma","volume":"514","author":"Chen","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/ni967","article-title":"The B7 family member B7-H3 preferentially down-regulates T helper type 1\u2013mediated immune responses","volume":"4","author":"Suh","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1016\/j.stem.2021.04.011","article-title":"CD276 expression enables squamous cell carcinoma stem cells to evade immune surveillance","volume":"28","author":"Wang","year":"2021","journal-title":"Cell Stem Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41388-018-0407-9","article-title":"Immunoregulatory protein B7-H3 regulates cancer stem cell enrichment and drug resistance through MVP-mediated MEK activation","volume":"38","author":"Liu","year":"2018","journal-title":"Oncogene"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1002\/pros.24180","article-title":"Immune checkpoint B7-H3 protein expression is associated with poor outcome and androgen receptor status in prostate cancer","volume":"81","author":"Kildal","year":"2021","journal-title":"Prostate"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1007\/s00259-020-05050-z","article-title":"IntraOmmaya compartmental radioimmunotherapy using 131I-omburtamab\u2014pharmacokinetic modeling to optimize therapeutic index","volume":"48","author":"Yerrabelli","year":"2020","journal-title":"Eur. J. Nucl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e004875","DOI":"10.1136\/jitc-2022-004875","article-title":"Genome-scale CRISPR\u2013Cas9 screen reveals novel regulators of B7-H3 in tumor cells","volume":"10","author":"Zhao","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.omto.2020.03.019","article-title":"B7-H3-Targeted CAR-T Cells Exhibit Potent Antitumor Effects on Hematologic and Solid Tumors","volume":"17","author":"Zhang","year":"2020","journal-title":"Mol. Ther.-Oncolytics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.omto.2019.07.002","article-title":"B7-H3 as a Novel CAR-T Therapeutic Target for Glioblastoma","volume":"14","author":"Tang","year":"2019","journal-title":"Mol. Ther.-Oncolytics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"17015","DOI":"10.1038\/sigtrans.2017.15","article-title":"Therapeutic potential of an anti-HER2 single chain antibody\u2013DM1 conjugates for the treatment of HER2-positive cancer","volume":"2","author":"Zhang","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1158\/2159-8290.CD-18-1522","article-title":"Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy","volume":"9","author":"Driehuis","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4367","DOI":"10.1158\/1078-0432.CCR-10-2811","article-title":"EGFR Signaling Regulates Tumor Cell Migration in Craniopharyngiomas","volume":"17","author":"Gebhardt","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"136","DOI":"10.31083\/j.fbl2704136","article-title":"Targeted Therapy in the Management of Modern Craniopharyngiomas","volume":"27","author":"Reyes","year":"2022","journal-title":"Front. Biosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1093\/neuonc\/noy035","article-title":"Multiplexed immunofluorescence reveals potential PD-1\/PD-L1 pathway vulnerabilities in craniopharyngioma","volume":"20","author":"Coy","year":"2018","journal-title":"Neuro Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e000406","DOI":"10.1136\/jitc-2019-000406","article-title":"Expression and clinical significance of PD-L1, B7-H3, B7-H4 and VISTA in craniopharyngioma","volume":"8","author":"Wang","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1126\/science.aar6711","article-title":"CAR T cell immunotherapy for human cancer","volume":"359","author":"June","year":"2018","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3322\/caac.21705","article-title":"Antibody\u2013drug conjugates: Smart chemotherapy delivery across tumor histologies","volume":"72","author":"Tarantino","year":"2021","journal-title":"CA A Cancer J. Clin."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7","DOI":"10.2217\/fon-2021-0550","article-title":"Trastuzumab deruxtecan for HER2+ advanced breast cancer","volume":"18","author":"Lee","year":"2022","journal-title":"Futur. Oncol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/12\/1744\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:25:35Z","timestamp":1760145935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/12\/1744"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,24]]},"references-count":28,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["biom12121744"],"URL":"https:\/\/doi.org\/10.3390\/biom12121744","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,24]]}}}