{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T23:21:04Z","timestamp":1792884064782,"version":"4.5.0"},"reference-count":57,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81802676"],"award-info":[{"award-number":["81802676"]}],"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":["31800752"],"award-info":[{"award-number":["31800752"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wuhan Youth Cadre Project","award":["2017zqnlxr01"],"award-info":[{"award-number":["2017zqnlxr01"]}]},{"name":"Wuhan Youth Cadre Project","award":["2017zqnlxr02"],"award-info":[{"award-number":["2017zqnlxr02"]}]},{"name":"Clinical Research Physician Program of Tongji Medical College","award":["5001540018"],"award-info":[{"award-number":["5001540018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chimeric antigen receptor T cells (CAR-Ts) have demonstrated remarkable efficacy in hematological cancers but have not yet translated in treating solid tumors. The significant hurdles limiting CAR-T therapy were from a paucity of differentially expressed cell surface molecules on solid tumors that can be safely targeted. Here, we present TSH receptor (TSHR) as a putative target for CAR-T therapy of differentiated thyroid cancer (DTC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We undertook a large-scale screen on thyroid cancer tissues and multiple internal organs through bioinformatical analysis and immunohistochemistry to date TSHR expression. Using 3 previously described monoclonal antibodies, we generated 3 third-generation CAR-Ts. We tested anti-TSHR CAR-T in vitro activity by T-cell function and killing assay. Then we tested preclinical therapeutical efficacy in a xenograft mouse model of DTC and analyzed mice\u2019s physical conditions and histological abnormalities to evaluate anti-TSHR CAR-T\u2019s safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TSHR is highly and homogeneously expressed on 90.8% (138\/152) of papillary thyroid cancer, 89.2% (33\/37) of follicular thyroid cancer, 78.2% (18\/23) of cervical lymph node metastases, and 86.7% of radioactive iodine resistance diseases. We developed 3 novel anti-TSHR CAR-Ts from monoclonal antibodies M22, K1-18, and K1-70; all 3 CAR-Ts mediate significant antitumor activity in vitro. Among these, we demonstrate that K1-70 CAR-T can have therapeutical efficacy in vivo, and no apparent toxicity has been observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TSHR is a latent target antigen of CAR-T therapy for DTC. Anti-TSHR CAR-T could represent a therapeutic option for patients with locoregional relapsed or distant metastases of thyroid cancer and should be tested in carefully designed clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgab819","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T06:30:12Z","timestamp":1636439412000},"page":"1110-1126","source":"Crossref","is-referenced-by-count":46,"title":["CAR-T Cells Targeting TSHR Demonstrate Safety and Potent Preclinical Activity Against Differentiated Thyroid Cancer"],"prefix":"10.1210","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6281-6994","authenticated-orcid":false,"given":"Hanning","family":"Li","sequence":"first","affiliation":[{"name":"Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei 430030, People\u2019s Republic of China"},{"name":"Laboratory 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