{
  "abstract": "Background Therapies that deliver deep and durable outcomes for patients with various types of solid tumors remain elusive, due in part to toxicities associated with target selection and a lack of appropriately specific antigens, alongside suppressive tumor microenvironments. Here we describe a novel two-component therapeutic regimen, DISP-10, which consists of a tumor specific and intravenously administered viral vector engineered to deliver a modified form of BCMA to solid tumors, and a well-characterized BCMA-directed CAR T cell. In addition to secreted and membrane-bound forms of the engineered BCMA target, the DISP-10 virus (DV-10) is also engineered to express IL18 and CXCL9 to enhance immune activation and infiltration to the TME. The combination is designed to deliver powerful anti-tumor responses from a BCMA CAR T, regardless of epithelial tumor subtype.Methods DV-10 was developed by insertion of BCMA, IL18, and CXCL9 transgenes into a tumor-specific, replication competent, and systemically administered adenovirus. Effective replication and transgene expression were confirmed in multiple tumor cell types. Combination activity of the virus and BCMA-specific CAR T cells was studied utilizing monolayer, tumor spheroid, and in vivo models with multiple data collection strategies.Results In preclinical models, we observed robust surface expression of the BCMA target antigen both in vitro and in vivo on infected tumor cells, along with CAR T cell activation and expansion, followed by tumor cell elimination. Labeling of both DV-10 infected and neighboring uninfected cells was observed, confirming localized spread of the target antigen. We also confirmed that successful viral replication and transgene expression was specifically limited to infected tumor cells but not normal cells, suggesting a strong safety and specificity profile for the combination treatment. Expression and function of IL18 and CXCL9 was also confirmed. Virus-mediated target delivery and subsequent recognition by CAR T cell led to a strong anti-tumor response across models, including NSG mouse models and primary human tumor samples.Conclusions Based on the promising preclinical efficacy and safety/specificity profile of this novel therapeutic, a Phase I study is planned to test this strategy in multiple solid tumors.",
  "authors": [
    {
      "affiliations": [
        "Dispatch Biotherapeutics, Philadelphia, PA, USA"
      ],
      "name": "Lisa Cucolo"
    },
    {
      "affiliations": [
        "Dispatch Biotherapeutics, San Francisco, CA, USA"
      ],
      "name": "Surabhi Srinivasan"
    },
    {
      "affiliations": [
        "Dispatch Biotherapeutics, Philadelphia, PA, USA"
      ],
      "name": "Tatiana M Garcia-Bates"
    },
    {
      "affiliations": [
        "Dispatch Biotherapeutics, Philadelphia, PA, USA"
      ],
      "name": "Nicholas Grams"
    },
    {
      "affiliations": [
        "Dispatch Biotherapeutics, Philadelphia, PA, USA"
      ],
      "name": "Rebecca M Broeckel"
    },
    {
      "affiliations": [
        "Dispatch Biotherapeutics, San Francisco, CA, USA"
      ],
      "name": "Dan Ilya Piraner"
    },
    {
      "affiliations": [
        "Dispatch Biotherapeutics, San Francisco, CA, USA"
      ],
      "name": "Weichao Zhuo"
    },
    {
      "affiliations": [
        "Dispatch Biotherapeutics, Philadelphia, PA, USA"
      ],
      "name": "Anna Wolfe"
    },
    {
      "affiliations": [
        "Dispatch Biotherapeutics, Philadelphia, PA, USA"
      ],
      "name": "Tyler T Fallon"
    },
    {
      "affiliations": [
        "Dispatch Biotherapeutics, Philadelphia, PA, USA"
      ],
      "name": "Patricia Brafford"
    },
    {
      "affiliations": [
        "Dispatch Biotherapeutics, Philadelphia, PA, USA"
      ],
      "name": "Maura Diamond"
    },
    {
      "affiliations": [
        "Dispatch Biotherapeutics, Philadelphia, PA, USA"
      ],
      "name": "Nishi Gheewala"
    },
    {
      "affiliations": [
        "Dispatch Biotherapeutics, San Francisco, CA, USA"
      ],
      "name": "Jerick Sanchez"
    },
    {
      "affiliations": [
        "Dispatch Biotherapeutics, San Francisco, CA, USA"
      ],
      "name": "Raymond Liu"
    },
    {
      "affiliations": [
        "Dispatch Biotherapeutics, Philadelphia, PA, USA"
      ],
      "name": "Jason L DeHart"
    },
    {
      "affiliations": [
        "Dispatch Biotherapeutics, San Francisco, CA, USA"
      ],
      "name": "Siler Panowski"
    },
    {
      "affiliations": [
        "Dispatch Biotherapeutics, San Francisco, CA, USA"
      ],
      "name": "Barbra J Sasu"
    },
    {
      "affiliations": [
        "Dispatch Biotherapeutics, Philadelphia, PA, USA"
      ],
      "name": "Lexus R Johnson"
    }
  ],
  "title": "393 DISP-10 is a novel CAR T and tumor-specific virus combination undergoing clinical development that is designed for use as a universal treatment for epithelial tumors",
  "uid": "6ae1500e-aac4-5c2d-82e8-9f93948a2acd"
}