{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:28:12Z","timestamp":1792787292472,"version":"4.5.0"},"reference-count":26,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T00:00:00Z","timestamp":1691020800000},"content-version":"unspecified","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Elios Therapeutics","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,6,28]]},"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is made by ex vivo priming matured autologous dendritic cells (DCs) with yeast cell wall particles (YCWPs) loaded with autologous tumor lysate (TL). The tumor lysate, particle only (TLPO) vaccine uses autologous TL-loaded YCWPs coated with silicate for in vivo DC loading. Here we report the 36-month prespecified analyses of this prospective, randomized, double-blind trial investigating the ability of the TLPO and TLPLDC (\u00b1granulocyte-colony stimulating factor (G-CSF)) vaccines to prevent melanoma recurrence in high-risk patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with clinically disease-free stage III\/IV melanoma were randomized 2:1 initially to TLPLDC versus placebo (n=124) and subsequently TLPO versus TLPLDC (n=63). All patients were randomized and blinded; however, the placebo control arm was replaced in the second randomization scheme with another novel vaccine; some analyses in this paper therefore reflect a combination of the two randomization schemes. Patients receiving the TLPLDC vaccine were further divided by their method of DC harvest (with or without G-CSF pretreatment); this was not randomized. The use of standard of care checkpoint inhibitors was not stratified between groups. Safety was assessed and Kaplan-Meier and log-rank analyses compared disease-free (DFS) and overall survival (OS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After combining the two randomization processes, a total of 187 patients were allocated between treatment arms: placebo (n=41), TLPLDC (n=103), or TLPO (n=43). The allocation among arms created by the addition of patients from the two separate randomization schemes does not reflect concurrent randomization among all treatment arms. TLPLDC was further divided by use of G-CSF in DC harvest: no G-CSF (TLPLDC) (n=47) and with G-CSF (TLPLDC+G) (n=56). Median follow-up was 35.8 months. Only two patients experienced a related adverse event \u2265grade 3, one each in the TLPLDC+G\u2009and placebo arms. DFS was 27.2% (placebo), 55.4% (TLPLDC), 22.9% (TLPLDC+G), and 60.9% (TLPO) (p&lt;0.001). OS was 62.5% (placebo), 93.6% (TLPLDC), 57.7% (TLPLDC+G), and 94.6% (TLPO) (p=0.002).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The TLPO and TLPLDC (without G-CSF) vaccines were associated with improved DFS and OS in this clinical trial. Given production and manufacturing advantages, the efficacy of the TLPO vaccine will be confirmed in a phase 3 trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT02301611\">NCT02301611<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2023-006665","type":"journal-article","created":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T13:30:58Z","timestamp":1691069458000},"page":"e006665","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":24,"title":["Prospective, randomized, double-blind phase 2B trial of the TLPO and TLPLDC vaccines to prevent recurrence of resected stage III\/IV melanoma: a prespecified 36-month analysis"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct02301611","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Elizabeth Lee","family":"Carpenter","sequence":"first","affiliation":[{"name":"Surgery, San Antonio Military Medical Center, Fort Sam Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5370-8991","authenticated-orcid":false,"given":"Spencer","family":"Van Decar","sequence":"additional","affiliation":[{"name":"Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra M","family":"Adams","sequence":"additional","affiliation":[{"name":"Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne E","family":"O\u2019Shea","sequence":"additional","affiliation":[{"name":"Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8805-8148","authenticated-orcid":false,"given":"Patrick","family":"McCarthy","sequence":"additional","affiliation":[{"name":"General Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert Connor","family":"Chick","sequence":"additional","affiliation":[{"name":"Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy Travis","family":"Clifton","sequence":"additional","affiliation":[{"name":"Surgery, Uniformed Services University, Bethesda, Maryland, USA"},{"name":"Surgical Oncology, Brooke Army Medical Center, Fort Sam Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4593-7502","authenticated-orcid":false,"given":"Timothy","family":"Vreeland","sequence":"additional","affiliation":[{"name":"Surgery, Uniformed Services University, Bethesda, Maryland, USA"},{"name":"Surgical Oncology, Brooke Army Medical Center, Fort Sam Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franklin A","family":"Valdera","sequence":"additional","affiliation":[{"name":"Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankur","family":"Tiwari","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Texas Health Sciences Center, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Hale","sequence":"additional","affiliation":[{"name":"Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA"},{"name":"Surgery, Uniformed Services University, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Kemp Bohan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelies","family":"Hickerson","sequence":"additional","affiliation":[{"name":"Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Smolinsky","sequence":"additional","affiliation":[{"name":"Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katryna","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Cindass","sequence":"additional","affiliation":[{"name":"Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hyngstrom","sequence":"additional","affiliation":[{"name":"Surgical Oncology, Huntsman Cancer Institute Cancer Hospital, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam C","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Surgery, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Jakub","sequence":"additional","affiliation":[{"name":"Surgery, Mayo Clinic, Jacksonville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey J","family":"Sussman","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montaser F","family":"Shaheen","sequence":"additional","affiliation":[{"name":"Medical Oncology, University of Arizona Medical Center-University Campus, Tucson, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianzhong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Clemson University, Clemson, South Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E","family":"Wagner","sequence":"additional","affiliation":[{"name":"Orbis Health Solutions, Greenville, South Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Faries","sequence":"additional","affiliation":[{"name":"Surgical Oncology, Cedars-Sinai Medical Center Angeles Clinic and Research Institute, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George E","family":"Peoples","sequence":"additional","affiliation":[{"name":"Cancer Vaccine Development Program, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,8,3]]},"reference":[{"key":"2025100313300084000_11.8.e006665.1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.clindermatol.2012.08.012","article-title":"Adjuvant Immunotherapy of Melanoma and development of new approaches using the Neoadjuvant approach","volume":"31","author":"Davar","year":"2013","journal-title":"Clin Dermatol"},{"key":"2025100313300084000_11.8.e006665.2","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12071994","article-title":"Adjuvant therapy for Melanoma: past, current, and future developments","volume":"12","author":"Testori","year":"2020","journal-title":"Cancers (Basel)"},{"key":"2025100313300084000_11.8.e006665.3","doi-asserted-by":"crossref","first-page":"6126","DOI":"10.1245\/s10434-021-09709-1","article-title":"A phase IIb randomized controlled trial of the TLPLDC vaccine as adjuvant therapy after surgical resection of stage III\/IV Melanoma: A primary analysis","volume":"28","author":"Vreeland","year":"2021","journal-title":"Ann Surg Oncol"},{"key":"2025100313300084000_11.8.e006665.4","doi-asserted-by":"publisher","DOI":"10.1177\/1758834015616934"},{"key":"2025100313300084000_11.8.e006665.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2018.03.005"},{"key":"2025100313300084000_11.8.e006665.6","doi-asserted-by":"crossref","DOI":"10.1186\/s13045-017-0552-6","article-title":"Cancer Immunotherapy beyond immune Checkpoint inhibitors","volume":"11","author":"Marin-Acevedo","year":"2018","journal-title":"J Hematol 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Cancer vaccines: should we be targeting patients with less aggressive disease? 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