{
  "abstract": "Background Prostate cancer is the most commonly diagnosed cancer in men in the USA after skin cancer, and the second most prevalent cancer in men globally. Despite the availability of treatment options including chemotherapy, androgen deprivation therapy, androgen receptor inhibitors, and novel immunotherapies, prostate cancer remains a formidable therapeutic challenge. To expand the current treatment arsenal, we developed a novel self-assembling cancer immunotherapeutic (SACI) platform. This platform comprises a Mycobacterium tuberculosis heat shock protein 70-avidin fusion protein (MAP), which serves as a broadly immune-activating adjuvant, and a biotinylated immunogenic protein targeting Prostate Stem Cell Antigen (PSCA), referred to as VTX-P04.Methods A biotinylated PSCA protein was used to generate VTX-P04 through self-assembly with MAP at a 1:1 molar ratio at room temperature. To evaluate antigen-specific immune responses, six- to eight-week-old male C57BL/6J mice were vaccinated intradermally in a prime-boost-boost regimen at two-week intervals. On week six, splenocytes and lymph node cells were harvested and analyzed via flow cytometry for PSCA-specific T cell responses. For the efficacy study, mice were inoculated subcutaneously with 5 × 10 6 TRAMP-C2 cells and received VTX-P04 vaccinations on days 7, 21, and 35 post-tumor implantation. Additionally, anti-PD-1 antibody was administered starting on day 7 intraperitoneally and continued biweekly. Tumor volumes were measured twice weekly using digital calipers, and survival was recorded until tumors reached 20 mm in diameter.Results VTX-P04 vaccination elicited robust antigen-specific immune responses. Significant increases in CD8 +IFNγ+ T cells were observed at VTX-P04 doses of 280 and 560 μg, and CD4+IFNγ+ T cells at 280 μg compared to saline-treated controls in both splenocytes and lymphocytes. In the tumor model, combinatorial treatment with VTX-P04 and anti-mPD1 significantly improved survival and slowed tumor growth. Mice receiving VTX-P04 at 140, 280, or 420 μg combined with anti-mPD1 demonstrated significantly prolonged overall survival (p < 0.001; Log-rank and Mantel-Cox tests) and reduced tumor volumes (ANOVA) compared to control mice.Conclusions Our findings demonstrate that VTX-P04 is well-tolerated and induces potent PSCA-specific T cell responses. When combined with anti-PD-1 therapy, VTX-P04 enhances survival and reduces tumor burden in a preclinical prostate cancer model. These results, along with our prior work on a Lassa fever vaccine, 1 support the potential of our SACI platform for application across infectious disease and oncology settings.Reference Leblanc P, et al. VaxCelerate II: rapid development of a self-assembling vaccine for lassa fever. Hum Vaccin Immunother. 2014;10(10):3022–38.",
  "authors": [
    {
      "affiliations": [
        "Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"
      ],
      "name": "Yohannes Gemechu"
    },
    {
      "affiliations": [
        "Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"
      ],
      "name": "Ugur Pala"
    },
    {
      "affiliations": [
        "Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"
      ],
      "name": "Jeffrey Gelfand"
    },
    {
      "affiliations": [
        "Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"
      ],
      "name": "Timothy A Brauns"
    },
    {
      "affiliations": [
        "Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"
      ],
      "name": "David E Kling"
    },
    {
      "affiliations": [
        "Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"
      ],
      "name": "Ann E Sluder"
    },
    {
      "affiliations": [
        "Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"
      ],
      "name": "Pierre R Leblanc"
    },
    {
      "affiliations": [
        "Voltron Therapeutics, Inc, New York, NY, USA"
      ],
      "name": "George Steinfels"
    },
    {
      "affiliations": [
        "Voltron Therapeutics, Inc, New York, NY, USA"
      ],
      "name": "Paul Korner"
    },
    {
      "affiliations": [
        "Voltron Therapeutics, Inc, New York, NY, USA"
      ],
      "name": "Ishan Kapila"
    },
    {
      "affiliations": [
        "Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"
      ],
      "name": "Patrick M Reeves"
    },
    {
      "affiliations": [
        "Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"
      ],
      "name": "Mark C Poznansky"
    }
  ],
  "title": "928 VTX-P04, a self-assembling immunotherapy targeting PSCA, induces T cell responses and inhibits TRAMP-C2 tumor growth in a C57BL/6 mouse model of prostate cancer",
  "uid": "7a02d2eb-1eec-5890-9dd2-b90231848801"
}