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While surgery offers a curative option, most patients present with advanced disease, for which current therapeutic options are ineffective. B7-H3 is an immune checkpoint molecule that is overexpressed in ICC relative to normal tissue, making it an attractive therapeutic target. Utilizing\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      models, we investigated the efficacy of a B7-H3-targeted CAR T to treat ICC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      B7-H3 CAR T cells were generated from peripheral blood mononuclear cells of normal donors, transduced with a retroviral vector encoding a second generation B7-H3 specific CAR construct, incorporating an inducible caspase9 (iCas9) suicide gene-based safety switch. The anti-tumor activity of iCas9.B7-H3 CAR T cells against ICC was tested\n                      <jats:italic>in vitro<\/jats:italic>\n                      using human ICC cell lines and patient-derived organotypic tumor spheroids (PDOTS) and\n                      <jats:italic>in vivo<\/jats:italic>\n                      using xenograft models of ICC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Human ICC cell lines, resected ICC samples from patients, and ICC tissue microarrays demonstrate homogeneous expression of B7-H3. iCas9.B7-H3 CAR T cells demonstrated potent anti-tumor activity\n                      <jats:italic>in vitro<\/jats:italic>\n                      against multiple patient-derived ICC cell lines. A single systemic dose of iCas9.B7-H3 CAR T cells induced complete and sustained eradication of orthotopic ICC tumors in a preclinical mouse model, even after tumor re-challenge. Locoregional delivery of CAR T cells via splenic and intra-tumoral injection was equally effective as systemic therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results provide a strong rationale for evaluating the iCas9.B7-H3 CAR T cell strategy in clinical trials for patients with advanced ICC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13046-026-03723-5","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T12:26:14Z","timestamp":1780575974000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["B7-H3 CAR T cells eradicate intrahepatic cholangiocarcinoma and induce durable response"],"prefix":"10.1186","volume":"45","author":[{"given":"Shahrzad","family":"Arya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Ventin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Cattaneo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Nebbia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Amir","family":"Sanatkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangjin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric A.","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabeel M.","family":"Bardeesy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Ting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikram","family":"Deshpande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Ryeom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soldano","family":"Ferrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina R.","family":"Ferrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"issue":"Suppl 1","key":"3723_CR1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1111\/liv.14095","volume":"39","author":"SA Khan","year":"2019","unstructured":"Khan SA, Tavolari S, Brandi G. 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