{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:47:58Z","timestamp":1788997678019,"version":"build-2803163510"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010711","name":"Sy\u00f6p\u00e4s\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017400","name":"Finnish Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017400","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003125","name":"Suomen Kulttuurirahasto","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003125","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009067","name":"K. 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Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Clear cell renal cell carcinoma (ccRCC) remains a significant therapeutic challenge due to its biological heterogeneity, variable clinical behavior, and limited efficacy of single-agent systemic therapies. Combination strategies targeting multiple tumor-promoting pathways may improve therapeutic outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated combination treatment strategies integrating targeted systemic drugs with oncolytic adenovirus therapy using representative patient-derived cancer cell (PDC) models. Anti-tumor efficacy and immune-mediated cytotoxicity were assessed to investigate treatment responses across different patient-derived models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Combination treatment enhanced anti-tumor activity compared with either monotherapy alone and promoted immune-mediated cytotoxicity involving CD8+ T cells and natural killer (NK) cells. Treatment responses varied across the three PDC models, reflecting interpatient heterogeneity and suggesting potential value for biomarker-guided patient stratification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings demonstrate the potential of combining targeted therapy with oncolytic virotherapy to overcome current therapeutic limitations in ccRCC. Moreover, the use of advanced three-dimensional human-relevant PDC models provides a scalable platform for evaluating combination therapies, supporting personalized treatment strategies, and facilitating the development of therapeutic approaches applicable to ccRCC and other cancer types.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1760889","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:32:40Z","timestamp":1786685560000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel therapeutic strategies for ccRCC through integration of systemic drug combinations and oncolytic adenovirus immunotherapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Michaela","family":"Feodoroff","sequence":"first","affiliation":[{"name":"Laboratory of Immunovirotherapy, Drug Research Program, University of Helsinki Faculty of Pharmacy","place":["Helsinki, 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