{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:18:33Z","timestamp":1792790313798,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,24]]},"group-title":"Cancer Biology","reference-count":45,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["K08 CA285941"],"award-info":[{"award-number":["K08 CA285941"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 CA278051"],"award-info":[{"award-number":["R01 CA278051"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30 CA014520"],"award-info":[{"award-number":["P30 CA014520"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Centennial Scholar Fund UWSMPH"},{"name":"Stand up to CancerStand up to Cancer\/Cancer Research United Kingdom"},{"name":"St. Baldrick\u2019s Foundation Empowering Pediatric Immunotherapy for Childhood Cancers (EPICC) Team grant","id":[{"id":"https:\/\/ror.org\/03h1gea69","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Midwest Athletes Against Childhood Cancer"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Non-irradiated or irradiated tumor cells were co-cultured with CAR T cells (1:1)\n                    <jats:italic>in vitro<\/jats:italic>\n                    and supernatant media was subsequently collected for cytokines analyses. CAR T cells\u2019 phenotypes were characterized by flow cytometry including checkpoint marker expression. Xenograft models of metastatic neuroblastoma were generated in NOD-\n                    <jats:italic>\n                      Rag1\n                      <jats:sup>null<\/jats:sup>\n                      IL2rg\n                      <jats:sup>null<\/jats:sup>\n                    <\/jats:italic>\n                    (NRG) mice. Tumor-bearing mice received 1.8 Gy of radiation delivered by\n                    <jats:sup>177<\/jats:sup>\n                    Lu-NM600 RPT five days after tumor implantation. Nine days after RPT, 4 x 10\n                    <jats:sup>6<\/jats:sup>\n                    CAR T cells were administered intravenously. To evaluate tumor burden, mice were imaged weekly for 4 weeks.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    In models of metastatic neuroblastoma,\n                    <jats:sup>177<\/jats:sup>\n                    Lu-NM600 RPT significantly increased overall survival when combined with CAR T cell therapy\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Pre-treatment of tumor cells with\n                    <jats:sup>177<\/jats:sup>\n                    Lu also significantly increased CAR T cell cytotoxicity while decreasing production of IL-4 and IL-10\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Co-culture of CAR T cells with irradiated tumors led to increases in PD-1\n                    <jats:sup>+<\/jats:sup>\n                    TIM3\n                    <jats:sup>+<\/jats:sup>\n                    LAG3\n                    <jats:sup>+<\/jats:sup>\n                    T cells, suggesting that further combination with immune checkpoint inhibitors may enhance clinical efficacy.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.16.751528","type":"posted-content","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:40:17Z","timestamp":1790293217000},"source":"Crossref","is-referenced-by-count":0,"title":["Low-dose radiopharmaceutical therapy enhances the efficacy of B7-H3 CAR T cells in murine metastatic neuroblastoma"],"prefix":"10.64898","author":[{"given":"Amanda G.","family":"Shea","sequence":"first","affiliation":[{"name":"Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Ollendorff","sequence":"additional","affiliation":[{"name":"Department of Human Oncology, University of Wisconsin School of Medicine and Public 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