{
  "abstract": "Background 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.Methods 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 µg) 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.Results 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 µg dose level, 67% at the 300 µg dose, and 40% at the 600 µg dose level. All participants at the 300 µg 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.Conclusions The tri-antigen vaccine appears safe and immunogenic. The intermediate dose (300 µg) 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.Trial registration number NCT02780401.",
  "authors": [
    {
      "affiliations": [
        "UW Medicine Cancer Vaccine Institute, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Sasha E Stanton"
    },
    {
      "affiliations": [
        "UW Medicine Cancer Vaccine Institute, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Denise L Cecil"
    },
    {
      "affiliations": [
        "University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USA"
      ],
      "name": "Howard H Bailey"
    },
    {
      "affiliations": [
        "UW Medicine Cancer Vaccine Institute, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Ying Liu"
    },
    {
      "affiliations": [
        "UW Medicine Cancer Vaccine Institute, University of Washington, Seattle, Washington, USA"
      ],
      "name": "William R Gwin"
    },
    {
      "affiliations": [
        "UW Medicine Cancer Vaccine Institute, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Andrew L Colveler"
    },
    {
      "affiliations": [
        "UW Medicine Cancer Vaccine Institute, University of Washington, Seattle, Washington, USA"
      ],
      "name": "John B Liao"
    },
    {
      "affiliations": [
        "University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USA",
        "Department of Internal Medicine, University of Wisconsin, Madison, Wisconsin, USA"
      ],
      "name": "Kari B Wisinski"
    },
    {
      "affiliations": [
        "University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USA"
      ],
      "name": "Lisa Barroilhet"
    },
    {
      "affiliations": [
        "University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USA"
      ],
      "name": "KyungMann Kim"
    },
    {
      "affiliations": [
        "University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USA"
      ],
      "name": "Thomas C Havighurst"
    },
    {
      "affiliations": [
        "University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USA"
      ],
      "name": "Katina DeShong"
    },
    {
      "affiliations": [
        "University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USA"
      ],
      "name": "Kyleigh Twaroski"
    },
    {
      "affiliations": [
        "UW Medicine Cancer Vaccine Institute, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Jennifer S Childs"
    },
    {
      "affiliations": [
        "Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, USA"
      ],
      "name": "Eileen Dimond"
    },
    {
      "affiliations": [
        "Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, USA"
      ],
      "name": "Margaret Wojtowicz"
    },
    {
      "affiliations": [
        "Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, USA"
      ],
      "name": "Brandy M Heckman-Stoddard"
    },
    {
      "affiliations": [
        "UW Medicine Cancer Vaccine Institute, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Mary L Disis"
    }
  ],
  "title": "Safety and immunogenicity of a tri-antigen vaccine targeting IGFBP-2, HER2, and IGF-IR in participants with non-metastatic breast cancer",
  "uid": "485401ca-baa7-5370-b94a-a1da524fcfe5"
}