{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T10:11:18Z","timestamp":1792836678771,"version":"4.5.0"},"reference-count":44,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"unspecified","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"US Army Department of Defense Prostate Cancer Research Program","award":["W81XWH-21-1-0270"],"award-info":[{"award-number":["W81XWH-21-1-0270"]}]},{"name":"NIH","award":["1S10 OD025225"],"award-info":[{"award-number":["1S10 OD025225"]}]},{"name":"NIH","award":["P30 CA014520"],"award-info":[{"award-number":["P30 CA014520"]}]},{"name":"NIH","award":["P50 CA269011"],"award-info":[{"award-number":["P50 CA269011"]}]},{"name":"Bristol Myers Squibb","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Madison Vaccines, Inc","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":[[2026,2,13]]},"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In murine studies, we demonstrated that a DNA vaccine encoding the androgen receptor (pTVG-AR) given prior to androgen deprivation elicited prostate tumor-infiltrating lymphocytes and an antitumor response. The current trial evaluated this approach, with or without programmed cell death protein-1 (PD-1) blockade, in patients with high-risk newly diagnosed prostate cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In the first stage of a two-stage protocol, 24 patients were randomized to treatment with (1) degarelix alone (n=6); (2) pTVG-AR followed by degarelix (n=9); or (3) pTVG-AR, degarelix and nivolumab (n=9), each delivered over 12 weeks prior to prostatectomy. The primary objectives were safety and pathological complete response or minimal residual disease (MRD). Secondary endpoints were residual cancer burden (RCB) &lt;0.25\u2009cm\n                      <jats:sup>3<\/jats:sup>\n                      and 1-year prostate-specific antigen (PSA) progression-free survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Adverse events were almost exclusively in Arm 3, attributed to nivolumab. One patient achieved MRD (Arm 2), and three patients had an RCB &lt;0.25\u2009cm\n                      <jats:sup>3<\/jats:sup>\n                      (all in Arm 2). At 1 year after surgery, the PSA progression-free survival rate was 33% (2\/6) in Arm 1, 89% (8\/9) in Arm 2, and 33% (3\/9) in Arm 3 (p=0.039). Tissue analysis at prostatectomy demonstrated reduced CD4+cells with a regulatory phenotype in patients in Arm 2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this first stage of a pilot study that awaits confirmation with larger numbers of patients, our results suggest that vaccination targeting AR given prior to androgen deprivation therapy might improve outcome for patients with high-risk prostate cancer. Contrary to our initial hypothesis, this was not improved with the addition of PD-1 blockade, possibly due to the activation of regulatory CD4+T cells.<\/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=\"NCT04989946\">NCT04989946<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-013790","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T14:00:16Z","timestamp":1772632816000},"page":"e013790","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Androgen deprivation, androgen receptor-targeted vaccination, and nivolumab in patients with high-risk localized prostate cancer"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct04989946","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"David","family":"Jarrard","sequence":"first","affiliation":[{"name":"Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Department of Urology, University of Wisconsin, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Eickhoff","sequence":"additional","affiliation":[{"name":"Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Department of Biostatistics, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos E","family":"Kyriakopoulos","sequence":"additional","affiliation":[{"name":"Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Department of Medicine, University of Wisconsin Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghwan","family":"Jeon","sequence":"additional","affiliation":[{"name":"Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso P","family":"Tonelli","sequence":"additional","affiliation":[{"name":"Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Johnson","sequence":"additional","affiliation":[{"name":"Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1471-6723","authenticated-orcid":false,"given":"Douglas G","family":"McNeel","sequence":"additional","affiliation":[{"name":"Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Department of Medicine, University of Wisconsin Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"2026090204551735000_14.3.e013790.1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"2026090204551735000_14.3.e013790.2","doi-asserted-by":"crossref","first-page":"E17","DOI":"10.5489\/cuaj.3163","article-title":"Predictors of time to biochemical recurrence in a radical prostatectomy cohort within the PSA-era","volume":"10","author":"Shahabi","year":"2016","journal-title":"Can Urol Assoc J"},{"key":"2026090204551735000_14.3.e013790.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)09408-4"},{"key":"2026090204551735000_14.3.e013790.4","doi-asserted-by":"crossref","unstructured":"Chi KN , Nguyen PL , Higano CS . 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