{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:11:44Z","timestamp":1788369104429,"version":"build-2803163510"},"reference-count":72,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"u.s. department of veterans affairs","doi-asserted-by":"publisher","award":["I01 BX003916, P50026787 (NIH\/NIDCR)"],"award-info":[{"award-number":["I01 BX003916, P50026787 (NIH\/NIDCR)"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U01CA233102"],"award-info":[{"award-number":["U01CA233102"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA014520"],"award-info":[{"award-number":["P30 CA014520"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Barbara A. Suran Comparative Research Endowment"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Rationale<\/jats:title>\n<jats:p>Murine syngeneic tumor models have revealed efficacious systemic antitumor responses following primary tumor <jats:italic>in situ<\/jats:italic> vaccination combined with targeted radionuclide therapy to secondary or metastatic tumors. Here we present studies on the safety and feasibility of this approach in a relevant translational companion dog model (n = 17 dogs) with advanced cancer.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>The three component of the combination immuno-radiotherapy approach were employed either separately or in combination in companion dogs with advanced stage cancer. <jats:italic>In situ<\/jats:italic> vaccination was achieved through the administration of hypofractionated external beam radiotherapy and intratumoral hu14.18-IL2 fusion immunocytokine injections to the index tumor. <jats:italic>In situ<\/jats:italic> vaccination was subsequently combined with targeted radionuclide therapy using a theranostic pairing of IV <jats:sup>86<\/jats:sup>Y-NM600 (for PET imaging and subject-specific dosimetry) and IV <jats:sup>90<\/jats:sup>Y-NM600 (therapeutic radionuclide) prescribed to deliver an immunomodulatory 2 Gy dose to all metastatic sites in companion dogs with metastatic melanoma or osteosarcoma. In a subset of dogs, immunologic parameters preliminarily assessed.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The components of the immuno-radiotherapy combination were well tolerated either alone or in combination, resulting in only transient low grade (1 or 2) adverse events with no dose-limiting events observed. In subject-specific dosimetry analyses, we observed <jats:sup>86<\/jats:sup>Y-NM600 tumor:bone marrow absorbed-dose differential uptakes \u22652 in 4 of 5 dogs receiving the combination, which allowed subsequent safe delivery of at least 2 Gy <jats:sup>90<\/jats:sup>Y-NM600 TRT to tumors. NanoString gene expression profiling and immunohistochemistry from pre- and post-treatment biopsy specimens provide evidence of tumor microenvironment immunomodulation by <jats:sup>90<\/jats:sup>Y-NM600 TRT.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The combination of external beam radiotherapy, intratumoral immunocytokine, and targeted radionuclide immuno-radiotherapy known to have activity against syngeneic melanoma in murine models is feasible and well tolerated in companion dogs with advanced stage, spontaneously arising melanoma or osteosarcoma and has immunomodulatory potential. Further studies evaluating the dose-dependent immunomodulatory effects of this immuno-radiotherapy combination are currently ongoing.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0255798","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T19:01:43Z","timestamp":1628794903000},"page":"e0255798","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":40,"title":["Safety and feasibility of an in situ vaccination and immunomodulatory targeted radionuclide combination immuno-radiotherapy approach in a comparative (companion dog) setting"],"prefix":"10.1371","volume":"16","author":[{"given":"Kara","family":"Magee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian R.","family":"Marsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle 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