{
  "abstract": "Cancer cells remodel their metabolic environment to disable infiltrating immune cells. Adenosine is a principal mediator of this immunosuppression, impairing the metabolism and effector functions of T and natural killer (NK) cells. Blocking adenosine receptors or production within a redundant signaling network leaves the metabolite itself intact and has shown limited clinical efficacy. Adenosine deaminase (ADA) instead converts adenosine into inosine, a metabolite that can fuel T cell metabolism. We engineered non-pathogenic, tumor-tropic Escherichia coli K-12 DH5α to surface-display ADA, confining this metabolic switch to the tumor, and co-displayed interleukin-12 (IL-12) to couple metabolic rescue to local immune stimulation. Bacteria-displayed ADA alone restored metabolic and proliferative fitness in adenosine-suppressed lymphocytes to baseline, whereas incorporation of IL-12 coupled this rescue to enhanced effector function. Across multiple preclinical models of hematologic and solid malignancies, the dual-function bacteria were well tolerated, enhanced tumor control, prolonged survival, and induced durable protective immunity against melanoma rechallenge. The bacteria were enriched at tumor sites, reactivated quiescent immune compartments in leukemia, enhanced CAR-NK cell tumor trafficking and activity in pancreatic cancer, and outperformed recombinant proteins in breast cancer. These findings establish a modular living immunotherapeutic strategy that couples a local extracellular metabolic switch with localized cytokine delivery.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 33,
  "authors": [
    {
      "name": "Rizwan Romee",
      "orcid": "0000-0001-9077-4736"
    },
    {
      "name": "Stephanie Sendker"
    },
    {
      "name": "Shaobo Yang",
      "orcid": "0009-0006-5257-6775"
    },
    {
      "name": "Eden Bobilev"
    },
    {
      "name": "Alice Chen"
    },
    {
      "name": "Fuguo Liu"
    },
    {
      "name": "Anna Bader"
    },
    {
      "name": "Xingyu Deng"
    },
    {
      "name": "Jenny Ho"
    },
    {
      "name": "Maily Nguyen"
    },
    {
      "name": "Michael James"
    },
    {
      "name": "Veronica Hui"
    },
    {
      "name": "Kate Marinchev",
      "orcid": "0009-0004-0647-0342"
    },
    {
      "name": "Andreia Maia",
      "orcid": "0000-0002-7860-6219"
    },
    {
      "name": "Castilleja Albert",
      "orcid": "0009-0007-1819-5183"
    },
    {
      "name": "Isabella Salinas"
    },
    {
      "name": "Ashley Hu"
    },
    {
      "name": "Alaa Kassim Ali"
    },
    {
      "name": "Jacqueline Garcia"
    },
    {
      "name": "Daniel DeAngelo",
      "orcid": "0000-0001-7865-2306"
    },
    {
      "name": "Mohammad Rashidian",
      "orcid": "0000-0002-3708-0038"
    },
    {
      "name": "Bartosz Grzywacz"
    },
    {
      "name": "Robert Soiffer"
    },
    {
      "name": "Jerome Ritz",
      "orcid": "0000-0001-5526-4669"
    },
    {
      "name": "Catherine Wu",
      "orcid": "0000-0002-3348-5054"
    },
    {
      "name": "John Koreth"
    },
    {
      "name": "Remy Dulery"
    },
    {
      "name": "Jose Cancelas",
      "orcid": "0000-0002-1291-7233"
    },
    {
      "name": "Roman Shapiro"
    },
    {
      "name": "Mounica Vallurupalli",
      "orcid": "0000-0002-1995-5283"
    },
    {
      "name": "Jiahe Li",
      "orcid": "0000-0002-9889-8546"
    },
    {
      "name": "Andrew Lane",
      "orcid": "0000-0001-7380-0226"
    },
    {
      "name": "Mubin Tarannum"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2gnp7dv40fr4f.bib",
  "cited_by": 0,
  "doi": "10.21203/rs.3.rs-11368155/v1",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13734254/",
  "id": "2gnp7dv40fr4f",
  "issns": [
    "2693-5015"
  ],
  "landing_url": "https://doi.org/10.21203/rs.3.rs-11368155/v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1305|Bacterial Cancer Therapy"
    ]
  ],
  "openalex": "W7224126622",
  "pdf_url": "https://www.researchsquare.com/article/rs-11368155/latest.pdf",
  "pmcid": "PMC13734254",
  "pmid": "42990820",
  "published": "2026-10-29",
  "publisher": "American Journal Experts",
  "ris": "https://research.draconitic.com/paper/2gnp7dv40fr4f.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:23:53Z",
      "native_id": "PMC13734254",
      "source": "pmc",
      "url": "https://doi.org/10.21203/rs.3.rs-11368155/v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1305|Bacterial Cancer Therapy",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "A living enzymatic adenosine switch couples metabolic rescue to IL-12-driven antitumor immunity",
  "title_text": "A living enzymatic adenosine switch couples metabolic rescue to IL-12-driven antitumor immunity",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:53Z",
  "url": "https://research.draconitic.com/paper/2gnp7dv40fr4f",
  "venue": "Research Square",
  "versions": []
}