{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T07:26:02Z","timestamp":1789802762323,"version":"4.0.1"},"reference-count":40,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T00:00:00Z","timestamp":1706832000000},"content-version":"unspecified","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015338","name":"Cancer Moonshot","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015338","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinigen","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"MD Anderson Cancer Center Support Grant","award":["CA016672"],"award-info":[{"award-number":["CA016672"]}]},{"name":"Bristol Myers-Squibb","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100030840","name":"Iovance Biotherapeutics","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100030840","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA101642"],"award-info":[{"award-number":["CA101642"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2024,1,9]]},"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tumor-infiltrating lymphocyte (TIL) therapy has shown efficacy in metastatic melanoma, non-small cell lung cancer, and other solid tumors. Our preclinical work demonstrated more robust CD8 predominant TIL production when agonistic anti-4-1BB and CD3 antibodies were used in early ex vivo TIL culture.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with treatment-refractory metastatic colorectal (CRC), pancreatic (PDAC) and ovarian (OVCA) cancers were eligible. Lymphodepleting chemotherapy was followed by infusion of ex vivo expanded TIL, manufactured at MD Anderson Cancer Center with IL-2 and agonistic stimulation of CD3 and 4-1BB (urelumab). Patients received up to six doses of high-dose IL-2 after TIL infusion. Primary endpoint was evaluation of objective response rate at 12 weeks using Response Evaluation Criteria in Solid Tumors version 1.1 with secondary endpoints including disease control rate (DCR), duration of response, progression-free survival (PFS), overall survival (OS), and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      17 patients underwent TIL harvest and 16 were treated on protocol (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03610490\">NCT03610490<\/jats:ext-link>\n                      ), including 8 CRC, 5 PDAC, and 3 OVCA patients. Median age was 57.5 (range 33\u201370) and 50% were females. Median number of lines of prior therapy was 2 (range 1\u20138). No responses were observed at 12 weeks. Ten subjects achieved at least one stable disease (SD) assessment for a DCR of 62.5% (95% CI 35.4% to 84.8%). Best response included prolonged SD in a patient with PDAC lasting 17 months. Median PFS and OS across cohorts were 2.53 months (95%\u2009CI 1.54 to 4.11) and 18.86 months (95%\u2009CI 4.86 to NR), respectively. Grade 3 or higher toxicities attributable to therapy were seen in 14 subjects (87.5%; 95%\u2009CI 61.7% to 98.4%). Infusion product analysis showed the presence of effector memory cells with high expression of CD39 irrespective of tumor type and low expression of checkpoint markers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TIL manufactured with assistance of 4-1BB and CD3 agonism is feasible and treatment is associated with no new safety signals. While no responses were observed, a significant portion of patients achieved SD suggesting early\/partial immunological effect. Further research is required to identify factors associated with resistance and functionally enhance T cells for a more effective therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2023-006822","type":"journal-article","created":{"date-parts":[[2024,2,3]],"date-time":"2024-02-03T00:45:16Z","timestamp":1706921116000},"page":"e006822","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":56,"title":["Efficacy and safety of autologous tumor-infiltrating lymphocytes in recurrent or refractory ovarian cancer, colorectal cancer, and pancreatic ductal adenocarcinoma"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct03610490","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03610490","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05361174","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04426669","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05470283","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03610490","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Rodabe","family":"Amaria","sequence":"first","affiliation":[{"name":"Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5377-135X","authenticated-orcid":false,"given":"Michael J","family":"Overman","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milind","family":"Javle","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara B","family":"Antonoff","sequence":"additional","affiliation":[{"name":"Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Wei D","family":"Tzeng","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A","family":"Wolff","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubham","family":"Pant","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Lito","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 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Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donastas","family":"Sakellariou-Thompson","sequence":"additional","affiliation":[{"name":"Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1317-9287","authenticated-orcid":false,"given":"Cara L","family":"Haymaker","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Andr\u00e9e","family":"Forget","sequence":"additional","affiliation":[{"name":"Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 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