{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T22:32:56Z","timestamp":1793745176179,"version":"4.6.1"},"reference-count":31,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"unspecified","delay-in-days":23,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Merck Sharp & Dohme LLC","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100000892","name":"Prostate Cancer Foundation","doi-asserted-by":"publisher","award":["2017 Challenge Award"],"award-info":[{"award-number":["2017 Challenge Award"]}],"id":[{"id":"10.13039\/100000892","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Defense Prostate Cancer Clinical Trials Consortium","award":["2017"],"award-info":[{"award-number":["2017"]}]},{"name":"Department of Defense Prostate Cancer Clinical Trials Consortium","award":["W81XWH-22-2-0014"],"award-info":[{"award-number":["W81XWH-22-2-0014"]}]},{"name":"NIH","award":["P30 CA014520"],"award-info":[{"award-number":["P30 CA014520"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,4,7]]},"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We previously reported a trial using pembrolizumab with a DNA vaccine encoding prostatic acid phosphatase (pTVG-HP) in patients with metastatic castration-resistant prostate cancer (mCRPC). Favorable clinical outcomes were associated with T-cell activation, suggesting immune response to vaccination was critical. In the current trial, we evaluated whether immunization with two vaccines, to broaden the T-cell response to other cancer-associated antigens, would elicit greater anti-tumor efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>60 patients with mCRPC were treated with vaccine on days 1 and 8 of a 3\u2009week cycle, with pembrolizumab given on day 1 of each cycle. Patients in Arm A (n=30) received pTVG-HP as the vaccine, and patients in Arm B (n=30) received pTVG-AR (encoding the ligand-binding domain of the androgen receptor) alternating with pTVG-HP every two cycles. After eight cycles (6 months), patients continued to receive pembrolizumab alone, with the option to receive further booster immunizations at prostate-specific antigen (PSA) progression. The primary objective was 6-month progression-free survival (PFS). Secondary objectives included safety, objective response rate, PSA response rate, overall survival (OS), and immunological evaluations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall median time to progression was 24 weeks (24 weeks Arm A, 24 weeks Arm B, p=0.80). The month 6 PFS rate was 51% in Arm A and 45% in Arm B. Median OS was 2.8 years (2.5 years Arm A, 3.7 years Arm B, p=0.16). 20% of patients in each arm experienced a PSA decline of &gt;50%. 20 patients (n=8\u2009Arm A, n=12\u2009Arm B) had measurable disease, and 6\/20 (30%) experienced a partial response. Eight patients received booster immunizations after 6 months, 3 of whom subsequently experienced a PSA decline. Three patients in Arm B experienced creatine kinase elevation with or without increased transaminases, which were not observed in Arm A. T cell immune responses to both antigens were detected in patients treated in Arm B.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Treatment with DNA vaccines and pembrolizumab demonstrated anti-tumor activity in terms of PSA declines and objective responses. The addition of pTVG-AR did not significantly increase measures of clinical efficacy; however, it was associated with a slight increase in toxicity to tissues that also express AR.<\/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=\"NCT04090528\">NCT04090528<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-014323","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T14:55:15Z","timestamp":1777042515000},"page":"e014323","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Phase 2 trial of pTVG-HP \u00b1 pTVG-AR DNA vaccines and pembrolizumab in patients with metastatic, castration-resistant prostate cancer (mCRPC)"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct04090528","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6452-7405","authenticated-orcid":false,"given":"Christos E","family":"Kyriakopoulos","sequence":"first","affiliation":[{"name":"Medicine, Hematology\/Oncology, UWCCC, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8966-7631","authenticated-orcid":false,"given":"Russell K","family":"Pachynski","sequence":"additional","affiliation":[{"name":"Medicine\/Oncology, Washington University School of Medicine, St Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens C","family":"Eickhoff","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso P","family":"Tonelli","sequence":"additional","affiliation":[{"name":"Medicine, University of Wisconsin Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghwan","family":"Jeon","sequence":"additional","affiliation":[{"name":"University of Wisconsin Carbone Cancer Center, 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":"Medicine, University of Wisconsin Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"2026042407550918000_14.4.e014323.1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"2026042407550918000_14.4.e014323.2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1159\/000546930","article-title":"Management of Metastatic Prostate Cancer","volume":"49","author":"von Amsberg","year":"2026","journal-title":"Oncol Res Treat"},{"key":"2026042407550918000_14.4.e014323.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1001294"},{"key":"2026042407550918000_14.4.e014323.4","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/s41391-024-00799-y","article-title":"A real-world experience of pembrolizumab monotherapy in microsatellite instability-high and\/or tumor mutation burden-high metastatic castration-resistant prostate cancer: outcome 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