{
  "abstract": "Background: Chimeric antigen receptor (CAR) T cell therapy has had clinical success in hematologic malignancies, but limited efficacy is seen in solid tumors. In this study, we investigated whether systemic CAR T cell therapy could be enhanced in metastatic models of neuroblastoma when combined with radiopharmaceutical therapy (RPT). Methods: Non-irradiated or irradiated tumor cells were co-cultured with CAR T cells (1:1) in vitro and supernatant media was subsequently collected for cytokines analyses. CAR T cell phenotypes were characterized by flow cytometry including checkpoint marker expression. Xenograft models of metastatic neuroblastoma were generated in NOD-Rag1nullIL2rgnull (NRG) mice. Tumor-bearing mice received 1.8 Gy of radiation delivered by 177Lu-NM600 RPT five days after tumor implantation. Nine days after RPT, CAR T cells were administered intravenously. To evaluate tumor burden, mice were imaged weekly for 4 weeks. Results: In models of metastatic neuroblastoma, 177Lu-NM600 RPT significantly increased overall survival when combined with CAR T cell therapy in vivo. Pre-treatment of tumor cells with 177Lu also significantly increased CAR T cell cytotoxicity while decreasing production of IL-4 and IL-10 in vitro. Co-culture of CAR T cells with irradiated tumors led to increases in PD-1+TIM3+LAG3+ T cells, suggesting that further combination with immune checkpoint inhibitors may enhance clinical efficacy. Conclusions: Our findings demonstrate that low-dose RPT can potentiate the anti-tumor efficacy of CAR T cells in metastatic neuroblastoma. To our knowledge, this is the first report of dosimetry-based RPT being combined with CAR T cells in a metastatic solid tumor setting. These findings underscore the potential of combining RPT and CAR T cells to overcome the unique challenges of solid tumors, particularly when treating metastatic disease.",
  "abstract_shown": true,
  "affiliations": [
    "University of Wisconsin Madison"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "name": "A. G. Shea"
    },
    {
      "name": "A. Ollendorff"
    },
    {
      "name": "A. Wilke"
    },
    {
      "name": "L. Shi"
    },
    {
      "name": "A. Erbe"
    },
    {
      "name": "I. H. Ansari"
    },
    {
      "name": "M. Bio Idrissou"
    },
    {
      "name": "O. Kwon"
    },
    {
      "name": "H. Comas Rojas"
    },
    {
      "name": "M. Barisa"
    },
    {
      "name": "J. Anderson"
    },
    {
      "name": "J. C. Eickhoff"
    },
    {
      "name": "I. Ong"
    },
    {
      "name": "R. Richards"
    },
    {
      "name": "P. M. Sondel"
    },
    {
      "name": "C. M. Capitini"
    },
    {
      "name": "R. Hernandez"
    },
    {
      "name": "B. P. Bednarz"
    },
    {
      "name": "J. P. Weichert"
    },
    {
      "name": "Z. S. Morris"
    },
    {
      "affs": [
        0
      ],
      "name": "Q. H. Sodji"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/22w6j6mzyh7mf.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.16.751528",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.16.751528v1.full",
  "id": "22w6j6mzyh7mf",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.16.751528v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7214152100",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.16.751528v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/22w6j6mzyh7mf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:24Z",
      "native_id": "10.64898/2026.09.16.751528",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.16.751528v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Low-dose radiopharmaceutical therapy enhances the efficacy of B7-H3 CAR T cells in murine metastatic neuroblastoma",
  "title_text": "Low-dose radiopharmaceutical therapy enhances the efficacy of B7-H3 CAR T cells in murine metastatic neuroblastoma",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:24Z",
  "url": "https://research.draconitic.com/paper/22w6j6mzyh7mf",
  "venue": "bioRxiv",
  "versions": []
}