{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T21:31:17Z","timestamp":1784928677974,"version":"3.55.0"},"reference-count":40,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"unspecified","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Wings Of Karen","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"WA Aisles Alliance","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"NIH","award":["UL1 TR002319"],"award-info":[{"award-number":["UL1 TR002319"]}]},{"name":"National Cancer Institute","award":["686K836"],"award-info":[{"award-number":["686K836"]}]},{"name":"National Cancer Institute","award":["HHSN261201200033I"],"award-info":[{"award-number":["HHSN261201200033I"]}]},{"name":"American Cancer Society Professorship","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Helen B. Slonaker Endowed Professor for Cancer Research","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":[[2026,4,7]]},"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ductal carcinoma in situ (DCIS) is a preinvasive form of breast cancer. Current treatment consists of surgery, radiation, and often systemic therapy exposing patients to unnecessary health risks. Vaccines targeting DCIS may be a way to intercept preinvasive lesions and prevent the development of invasive breast cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a Th1 selective multiantigen, polyepitope plasmid-DNA vaccine encoding segments of IGFBP-2, HER2, and IGF-IR, all antigens expressed in hormone receptor positive and negative DCIS. We then performed a Phase I study in participants with non-metastatic breast cancer with no evidence of disease. The primary objective was to assess the safety of 3 monthly intradermal doses (150, 300, or 600 \u00b5g) of the tri-antigen vaccine with granulocyte macrophage colony-stimulating factor as an adjuvant. 32 participants were enrolled, 10 per dose level. Toxicity evaluations occurred monthly with vaccination and at 1 and 6 months after the last vaccine. Blood was collected at baseline and at 1 and 6 months after the last immunization to assess cellular immune responses. Participants were followed annually for 5 years for long-term toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>There was no significant difference in adverse events (AEs) across dose levels and all related AEs were grades 1 or 2. All doses were immunogenic; responders included 70% of participants at the 150 \u00b5g dose level, 67% at the 300 \u00b5g dose, and 40% at the 600 \u00b5g dose level. All participants at the 300 \u00b5g dose retained significant Th1-antigen-specific immune response at 6 months after end of immunizations. T-cells derived from vaccine immunologic responders exhibited gene expression profiles that indicated an increased metabolic fitness as compared with immunologic non-responders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The tri-antigen vaccine appears safe and immunogenic. The intermediate dose (300 \u00b5g) was chosen as the Phase II dose due to the long-term persistence of immunity after vaccination. The vaccine will be studied in Phase II trials for the treatment of DCIS.<\/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=\"NCT02780401\">NCT02780401<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-014314","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:15:19Z","timestamp":1777914919000},"page":"e014314","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Safety and immunogenicity of a tri-antigen vaccine targeting IGFBP-2, HER2, and IGF-IR in participants with non-metastatic breast cancer"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct02780401","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02780401","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4300-551X","authenticated-orcid":false,"given":"Sasha E","family":"Stanton","sequence":"first","affiliation":[{"name":"UW Medicine Cancer Vaccine Institute, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9923-3618","authenticated-orcid":false,"given":"Denise L","family":"Cecil","sequence":"additional","affiliation":[{"name":"UW Medicine Cancer Vaccine Institute, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard H","family":"Bailey","sequence":"additional","affiliation":[{"name":"University of Wisconsin Carbone Cancer Center, Madison, 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