{"doi":"10.1186/s13046-025-03475-8","title":"B7-H3 and CSPG4-targeted CAR T cells as potent effectors in anaplastic thyroid cancer","abstract":"BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare and aggressive malignancy with poor survival and no available effective therapy. This unmet clinical need led us to investigate chimeric antigen receptor (CAR) T cells s as potential treatment option for this malignant disease. As target tumor antigens of our CAR T cell therapy, we selected the chondroitin sulfate proteoglycan 4 (CSPG4) and the B7-homolog 3 (B7-H3), as they are both highly and homogeneously expressed on different types of thyroid carcinoma cell lines and tissues, including ATC. Importantly, both CSPG4 and B7-H3 have a low distribution on normal tissues, thus limiting 'on-target off-tumor' CAR T-related toxicities. METHODS: We generated CSPG4-specific and B7-H3-specific CAR T cells by utilizing a second-generation CAR construct comprised of a CD28 costimulatory domain and tested their antitumor activity in vitro and in an orthotopic xenograft murine model of ATC. RESULTS: We demonstrated that thyroid cancer cells are specifically recognized and effectively eradicated in vitro by CSPG4-targeted and B7-H3-targeted CAR T cells. Additionally, both CAR T cell types were able to mediate significant control or complete eradication of primary ATC tumors when mice were treated with CSPG4 CAR T cells or B7-H3 CAR T cells, respectively. CONCLUSION: Overall, in this study we identified CSPG4 and B7-H3 as valuable target antigens in thyroid cancer and demonstrated that CAR T cell immunotherapy can be a valuable therapeutic option for ATC patients. Our findings provide the translational basis for exploring CAR T cell immunotherapies targeting CSPG4 and B7-H3 with ATC patients who do not respond or relapse after first line treatment.","journal":"Journal of Experimental & Clinical Cancer Research","year":2025,"id":531686,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9643,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1034437,"name":"Marco Ventin","orcid":"0000-0002-4201-7009","position":1,"is_corresponding":false},{"id":1034435,"name":"Shahrzad Arya","orcid":"0009-0002-2451-7584","position":2,"is_corresponding":false},{"id":1412500,"name":"Cedric Bailey","orcid":"0000-0002-5674-5509","position":3,"is_corresponding":false},{"id":1129310,"name":"Venkata R. Vantaku","orcid":"0000-0003-2846-8716","position":4,"is_corresponding":false},{"id":1034434,"name":"Jingyu Jia","orcid":"0000-0001-7128-2621","position":5,"is_corresponding":false},{"id":1412501,"name":"Maoyang Qi","orcid":"0009-0000-8971-666X","position":6,"is_corresponding":false},{"id":375912,"name":"Luke Maggs","orcid":"0000-0001-5588-0103","position":7,"is_corresponding":false},{"id":1213793,"name":"Xinhui Wang","orcid":"0000-0002-4109-5793","position":8,"is_corresponding":false},{"id":858708,"name":"Sareh Parangi","orcid":"0000-0003-1280-2812","position":9,"is_corresponding":false},{"id":247569,"name":"Soldano Ferrone","orcid":"0000-0003-2900-8834","position":10,"is_corresponding":false},{"id":15997,"name":"Cristina R. Ferrone","orcid":"0000-0002-6295-1085","position":11,"is_corresponding":false},{"id":15976,"name":"Giulia Cattaneo","orcid":"0000-0002-7053-3238","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T02:51:18.928280Z","pmid":"40847369","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}