{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:48:00Z","timestamp":1788317280532,"version":"build-2803163510"},"reference-count":22,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T00:00:00Z","timestamp":1620864000000},"content-version":"unspecified","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA223484, U01CA233100, and U01CA244452."],"award-info":[{"award-number":["R01CA223484, U01CA233100, and U01CA244452."]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000892","name":"Prostate Cancer Foundation","doi-asserted-by":"publisher","award":["Prostate Cancer Foundation Challenge Grant"],"award-info":[{"award-number":["Prostate Cancer Foundation Challenge Grant"]}],"id":[{"id":"10.13039\/100000892","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2021,4,1]]},"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Sipuleucel-T is a US Food and Drug Administration-approved autologous cellular immunotherapy that improves survival in patients with metastatic castration-resistant prostate cancer (mCRPC). We examined whether administering ipilimumab after sipuleucel-T could modify immune and\/or clinical responses to this treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A total of 50 patients with mCRPC were enrolled into a clinical trial (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT01804465\">NCT01804465<\/jats:ext-link>, ClinicalTrials.gov) where they received ipilimumab either immediately or delayed 3 weeks following completion of sipuleucel-T treatment. Blood was collected at various timepoints of the study. Luminex assay for anti-prostatic acid phosphatase (PAP) and anti-PA2024-specific serum immunoglobulin G (IgG) and ELISpot for interferon-\u03b3 (IFN-\u03b3) production against PAP and PA2024 were used to assess antigen-specific B and T cell responses, respectively. Clinical response was defined as &gt;30% reduction in serum prostate-specific antigen levels compared with pretreatment levels. The frequency and state of circulating immune cells were determined by mass cytometry by time-of-flight and statistical scaffold analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We found the combination to be well tolerated with no unexpected adverse events occurring. The timing of ipilimumab did not significantly alter the rates of antigen-specific B and T cell responses, the primary endpoint of the clinical trial. Clinical responses were observed in 6 of 50 patients, with 3 having responses lasting longer than 3 months. The timing of ipilimumab did not significantly associate with clinical response or toxicity. The combination treatment did induce CD4 and CD8 T cell activation that was most pronounced with the immediate schedule. Lower frequencies of CTLA-4 positive circulating T cells, even prior to treatment, were associated with better clinical outcomes. Interestingly, these differences in CTLA-4 expression were associated with prior localized radiation therapy (RT) to the prostate or prostatic fossa. Prior radiation treatment was also associated with improved radiographic progression-free survival.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Combining CTLA-4 blockade with sipuleucel-T resulted in modest clinical activity. The timing of CTLA-4 blockade following sipuleucel-T did not alter antigen-specific responses. Clinical responses were associated with both lower baseline frequencies of CTLA-4 expressing T cells and a history of RT. Prior cancer therapy may therefore result in long-lasting immune changes that influence responsiveness to immunotherapy with sipuleucel-T and anti-CTLA-4.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2020-002254","type":"journal-article","created":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T13:07:05Z","timestamp":1620911225000},"page":"e002254","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":48,"title":["Pre-existing immune status associated with response to combination of sipuleucel-T and ipilimumab in patients with metastatic castration-resistant prostate cancer"],"prefix":"10.1136","volume":"9","clinical-trial-number":[{"clinical-trial-number":"nct01804465","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01804465","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4008-4080","authenticated-orcid":false,"given":"Meenal","family":"Sinha","sequence":"first","affiliation":[{"name":"Department Hematology\/Oncology, School of Medicine, University of California San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department Hematology\/Oncology, School of Medicine, University of California San Francisco, San Francisco, California, USA"},{"name":"Department of Epidemiology and Biostatistics, School of Medicine, University of California San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit","family":"Subudhi","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center Division of Cancer Medicine, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Chen","sequence":"additional","affiliation":[{"name":"Department Hematology\/Oncology, School of Medicine, University of California San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaqueline","family":"Marquez","sequence":"additional","affiliation":[{"name":"Department Hematology\/Oncology, School of Medicine, University of California San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric V","family":"Liu","sequence":"additional","affiliation":[{"name":"Department Hematology\/Oncology, School of Medicine, University of California San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Allaire","sequence":"additional","affiliation":[{"name":"Department Hematology\/Oncology, School of Medicine, University of California San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department Hematology\/Oncology, School of Medicine, University of California San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Ng","sequence":"additional","affiliation":[{"name":"Department Hematology\/Oncology, School of Medicine, University of California San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department Hematology\/Oncology, School of Medicine, University of California San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence W","family":"Friedlander","sequence":"additional","affiliation":[{"name":"Department Hematology\/Oncology, School of Medicine, University of California San Francisco, San Francisco, California, USA"},{"name":"Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"Department Hematology\/Oncology, School of Medicine, University of California San Francisco, San Francisco, California, USA"},{"name":"Helen Diller Family Comprehensive Cancer Center, 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