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Since anti\u2010CTLA\u20104 antibodies block immunosuppressive signals mainly in the lymph nodes (LNs), efficient drug delivery to the lymphatic system is desirable. However, the immune checkpoint inhibitors, especially anti\u2010CTLA\u20104 are currently administered intravenously (i.v.), resulting in limited efficacy in controlling solid tumor and inhibiting metastases, and the method of administration has not been optimized. Here, we show that a combination of local radiotherapy and administration of anti\u2010CTLA\u20104 antibodies using a lymphatic drug delivery system (LDDS) suppresses solid tumor and metastases. We compared the efficacy of LDDS\u2010based immunotherapy or radioimmunotherapy with i.v. administration in a solid\u2010tumor model created by subcutaneous inoculation into LN\u2010swollen mice with osteosarcoma cells. Tumor\u2010bearing mice were divided into various groups (no treatment, immunotherapy [i.v. or LDDS], radiotherapy, and radioimmunotherapy [i.v. or LDDS]) and were observed for 28\u2009days. Immunotherapy was administered with a cumulative dose of 10\u2009mg\/kg of anti\u2010CTLA\u20104 monoclonal antibody, and radiotherapy was administered with a cumulative 8\u2009Gy of fractionated X\u2010ray irradiation. For immunotherapy alone, LDDS provided slight tumor growth inhibition but did not inhibit distant metastasis. For radioimmunotherapy, however, tumor growth was delayed and distant metastasis was suppressed compared with radiotherapy alone. In particular, the LDDS group achieved a high tumor\u2010suppressive effect with T cell\u2010mediated immune activity, indicating the efficacy of LDDS in radioimmunotherapy.<\/jats:p>","DOI":"10.1111\/cas.16369","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T04:39:32Z","timestamp":1728448772000},"page":"4021-4033","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A combination of lymphatic drug delivery of anti\u2010<scp>CTLA<\/scp>\u20104 antibody and local radiotherapy for solid\u2010tumor treatment"],"prefix":"10.1111","volume":"115","author":[{"given":"Koki","family":"Takagi","sequence":"first","affiliation":[{"name":"Laboratory of Biomedical Engineering for Cancer, Graduate School of Biomedical Engineering Tohoku University  Sendai Miyagi 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Tohoku University  Sendai Miyagi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiro","family":"Mori","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Engineering for Cancer, Graduate School of Biomedical Engineering Tohoku University  Sendai Miyagi Japan"},{"name":"Division of Oral and Maxillofacial Oncology and Surgical Sciences, Graduate School of Dentistry Tohoku University  Sendai Miyagi Japan"},{"name":"Biomedical Engineering Cancer Research Center, Graduate School of Biomedical Engineering Tohoku University  Sendai Miyagi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4727-9558","authenticated-orcid":false,"given":"Tetsuya","family":"Kodama","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Engineering for Cancer, Graduate School of Biomedical Engineering Tohoku University  Sendai Miyagi Japan"},{"name":"Biomedical Engineering Cancer Research Center, 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