{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T08:10:06Z","timestamp":1792138206158,"version":"4.4.0"},"reference-count":28,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"unspecified","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","award":["23 3235 S and 21 1695 Pj"],"award-info":[{"award-number":["23 3235 S and 21 1695 Pj"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Assar Gabrielsson Foundation","award":["FB18-78"],"award-info":[{"award-number":["FB18-78"]}]},{"DOI":"10.13039\/100016669","name":"Sj\u00f6bergstiftelsen","doi-asserted-by":"publisher","award":["2024-985"],"award-info":[{"award-number":["2024-985"]}],"id":[{"id":"10.13039\/100016669","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Lion\u2019s Cancer Foundation West","award":["2019:16"],"award-info":[{"award-number":["2019:16"]}]},{"name":"King Gustav V Jubilee Clinic Cancer Research Foundation","award":["2024:578"],"award-info":[{"award-number":["2024:578"]}]},{"DOI":"10.13039\/501100006310","name":"Medicinska Forskningsr\u00e5det","doi-asserted-by":"publisher","award":["2023-02285"],"award-info":[{"award-number":["2023-02285"]}],"id":[{"id":"10.13039\/501100006310","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004176","name":"Miltenyi Biotec","doi-asserted-by":"publisher","award":["20200824_080232"],"award-info":[{"award-number":["20200824_080232"]}],"id":[{"id":"10.13039\/501100004176","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017138","name":"Health and Medical Care Committee of the Regional Executive Board, Region V\u00e4stra G\u00f6taland","doi-asserted-by":"publisher","award":["ALFGBG-1006284 and ALFGBG-1006739"],"award-info":[{"award-number":["ALFGBG-1006284 and ALFGBG-1006739"]}],"id":[{"id":"10.13039\/100017138","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Family Erling Persson Foundation","award":["2023 0076"],"award-info":[{"award-number":["2023 0076"]}]},{"DOI":"10.13039\/501100003849","name":"IngaBritt och Arne Lundbergs Forskningsstiftelse","doi-asserted-by":"publisher","award":["LU2019-0063"],"award-info":[{"award-number":["LU2019-0063"]}],"id":[{"id":"10.13039\/501100003849","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,2,10]]},"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Uveal melanoma is a rare melanoma subtype characterized by a liver-dominant pattern of metastasis which is associated with a lack of durable responses to immunotherapies. Adoptive cell transfer of autologous tumor-infiltrating lymphocytes (TILs) has been shown to induce responses in a subset of patients with metastatic uveal melanoma. The safety and feasibility of locoregional administration of TIL therapy via hepatic arterial infusion (HAI) have not previously been evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>\n                      This prospective, open-label, phase I trial investigated the safety and feasibility of one-time TIL therapy administered via HAI in patients with liver metastases of uveal melanoma. Preconditioning chemotherapy with melphalan (1\u2009mg\/kg, intravenous) was administered on day \u22125. TILs were delivered via percutaneous catheterization of the hepatic artery according to a dose escalation scheme (0.1, 0.3, or 1\u00d710\n                      <jats:sup>9<\/jats:sup>\n                      cells) on day 0. Patients received daily subcutaneous interleukin-2 (IL-2, 2 MIU) up to 14 days after TIL administration. The primary endpoint was the incidence and severity of adverse events (AEs). Secondary endpoints included clinical efficacy and the feasibility of TIL production using a semiautomated manufacturing system.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Six patients received TIL therapy manufactured using the CliniMACS Prodigy platform; five were treated according to protocol, while one received a lower TIL dose than planned. All had received prior systemic treatment. No AEs related to the HAI procedure were observed. All patients experienced grade \u22653 hematologic AEs related to preconditioning chemotherapy, and two patients experienced grade \u22653 AEs attributed to TIL\/IL-2. Best overall response was stable disease in all patients (100%). Median progression-free survival was 4 months, and median overall survival was 14 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TILs can be manufactured using the CliniMACS Prodigy. Administration of TIL via HAI was safe and feasible in patients with liver-dominant metastatic uveal melanoma. The used regimen appears insufficient to achieve durable clinical efficacy and implies a need for further testing to obtain conclusive results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration numbers<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04812470\">NCT04812470<\/jats:ext-link>\n                      , EUCT number: 2024-512877-28-00, EudraCT number: 2020-006126-31.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-014401","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T21:10:49Z","timestamp":1773868249000},"page":"e014401","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Phase I trial of locoregional administration of autologous tumor-infiltrating lymphocytes in patients with uveal melanoma and liver metastases (the HAITILS trial)"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct04812470","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8898-8301","authenticated-orcid":false,"given":"Axel","family":"Nelson","sequence":"first","affiliation":[{"name":"Department of Oncology, Institute of Clinical Sciences, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden"},{"name":"Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Riise","sequence":"additional","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Surgery, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Als\u00e9n","sequence":"additional","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Surgery, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wong","sequence":"additional","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Surgery, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden"},{"name":"Department of Radiology, Sahlgrenska University Hospital, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Carlson","sequence":"additional","affiliation":[{"name":"Department of Radiology, Sahlgrenska University Hospital, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Edman","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Holgersson","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden"},{"name":"Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5795-0355","authenticated-orcid":false,"given":"Roger","family":"Olofsson Bagge","sequence":"additional","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Surgery, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden"},{"name":"Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iva","family":"Johansson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Sahlgrenska Academy, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May","family":"Sadik","sequence":"additional","affiliation":[{"name":"Department of Clinical Physiology, Sahlgrenska Academy, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Edenbrandt","sequence":"additional","affiliation":[{"name":"Department of Clinical Physiology, Sahlgrenska Academy, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5222-7210","authenticated-orcid":false,"given":"Lisa M","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Surgery, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0346-6837","authenticated-orcid":false,"given":"Jonas A","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Surgery, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Ny","sequence":"additional","affiliation":[{"name":"Department of Oncology, Institute of Clinical Sciences, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden"},{"name":"Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"2026031814103417000_14.3.e014401.1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.123.12.1639"},{"key":"2026031814103417000_14.3.e014401.2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz176"},{"key":"2026031814103417000_14.3.e014401.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2103485"},{"key":"2026031814103417000_14.3.e014401.4","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.00605"},{"key":"2026031814103417000_14.3.e014401.5","doi-asserted-by":"publisher","DOI":"10.1200\/jco.20.00550"},{"key":"2026031814103417000_14.3.e014401.6","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-021-25332-w","article-title":"The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma","volume":"12","author":"Ny","year":"2021","journal-title":"Nat Commun"},{"key":"2026031814103417000_14.3.e014401.7","doi-asserted-by":"publisher","DOI":"10.1200\/jco.22.01705"},{"key":"2026031814103417000_14.3.e014401.8","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1097\/SLA.0000000000006255","article-title":"Survival and Quality of Life After Isolated Hepatic Perfusion With Melphalan as a Treatment for Uveal Melanoma Liver Metastases: Final Results From the Phase III Randomized Controlled Trial SCANDIUM","volume":"282","author":"Olofsson Bagge","year":"2025","journal-title":"Ann Surg"},{"key":"2026031814103417000_14.3.e014401.9","doi-asserted-by":"crossref","DOI":"10.1016\/j.annonc.2025.09.071","article-title":"LBA59 Combined percutaneous hepatic perfusion with ipilimumab plus nivolumab in metastatic uveal melanoma (CHOPIN): A single-center, open-label, randomized, phase II study","volume":"36","author":"Kapiteijn","year":"2025","journal-title":"Ann Oncol"},{"key":"2026031814103417000_14.3.e014401.10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2210233"},{"key":"2026031814103417000_14.3.e014401.11","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1136\/jitc-2022-005755","article-title":"Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study","volume":"10","author":"Chesney","year":"2022","journal-title":"J Immunother Cancer"},{"key":"2026031814103417000_14.3.e014401.12","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30251-6"},{"key":"2026031814103417000_14.3.e014401.13","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.91705.3","article-title":"Patient-derived xenografts and single-cell sequencing identifies three subtypes of tumor-reactive lymphocytes in uveal melanoma metastases","volume":"12","author":"Karlsson","year":"2024","journal-title":"Elife"},{"key":"2026031814103417000_14.3.e014401.14","doi-asserted-by":"crossref","DOI":"10.1186\/1479-5876-10-169","article-title":"Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients","volume":"10","author":"Ellebaek","year":"2012","journal-title":"J Transl Med"},{"key":"2026031814103417000_14.3.e014401.15","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-017-00786-z","article-title":"Clinical responses to adoptive T-cell transfer can be modeled in an autologous immune-humanized mouse model","volume":"8","author":"Jespersen","year":"2017","journal-title":"Nat Commun"},{"key":"2026031814103417000_14.3.e014401.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"2026031814103417000_14.3.e014401.17","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s00270-019-02198-6","article-title":"Feasibility of Yttrium-90 Radioembolization Dose Calculation Utilizing Intra-procedural Open Trajectory Cone Beam CT","volume":"43","author":"O\u2019Connor","year":"2020","journal-title":"Cardiovasc Intervent Radiol"},{"key":"2026031814103417000_14.3.e014401.18","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-025-88625-w","article-title":"18F-FDG PET\/CT assessment of metabolic tumor burden predicts survival in patients with metastatic posterior uveal melanoma","volume":"15","author":"Hindso","year":"2025","journal-title":"Sci Rep"},{"key":"2026031814103417000_14.3.e014401.19","doi-asserted-by":"publisher","DOI":"10.1097\/00002371-200309000-00001"},{"key":"2026031814103417000_14.3.e014401.20","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-1421"},{"key":"2026031814103417000_14.3.e014401.21","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0116"},{"key":"2026031814103417000_14.3.e014401.22","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2020-001743","article-title":"Comparison of non-myeloablative lymphodepleting preconditioning regimens in patients undergoing adoptive T cell therapy","volume":"9","author":"Nissani","year":"2021","journal-title":"J Immunother Cancer"},{"key":"2026031814103417000_14.3.e014401.23","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2025.2546402","article-title":"Lymphodepletion, tumor-infiltrating lymphocytes, and high versus low dose IL-2 followed by pembrolizumab in patients with metastatic melanoma","volume":"14","author":"Hasanov","year":"2025","journal-title":"Oncoimmunology"},{"key":"2026031814103417000_14.3.e014401.24","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.5449"},{"key":"2026031814103417000_14.3.e014401.25","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-19-3269"},{"key":"2026031814103417000_14.3.e014401.26","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.7150\/thno.79976","article-title":"In vivo imaging of CD8(+) T cells in metastatic cancer patients: first clinical experience with simultaneous [(89)Zr]Zr-Df-IAB22M2C PET\/MRI","volume":"13","author":"Schwenck","year":"2023","journal-title":"Theranostics"},{"key":"2026031814103417000_14.3.e014401.27","doi-asserted-by":"crossref","first-page":"1483254","DOI":"10.3389\/fimmu.2024.1483254","article-title":"Clinical-scale, modular manufacturing of tumor-reactive TILs using a closed and automated culture system","volume":"15","author":"V\u00f6lzke","year":"2024","journal-title":"Front Immunol"},{"key":"2026031814103417000_14.3.e014401.28","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15606-0"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2025-014401","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T21:10:53Z","timestamp":1773868253000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2025-014401"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":28,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3,18]]},"published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1136\/jitc-2025-014401"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2025-014401","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]}}}