{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T11:03:16Z","timestamp":1781348596484,"version":"3.54.1"},"reference-count":41,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,7,5]],"date-time":"2019-07-05T00:00:00Z","timestamp":1562284800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Human T cell lymphotropic virus 1 (HTLV\u20101)\u2010associated myelopathy\/tropical spastic paraparesis (HAM\/TSP) is a chronic, progressive, neurological disease. Chronic activation of CD8<jats:sup>+<\/jats:sup> T cells, as evidenced by increased spontaneous lymphoproliferation and HTLV\u20101\u2010specific cytotoxic T cells, has been demonstrated in HAM\/TSP patients. Since IL\u20102 and IL\u201015 stimulate memory CD8<jats:sup>+<\/jats:sup> T cell activity, these cytokines have been implicated in the immunopathogenesis of HAM\/TSP. In this phase I trial, we evaluated the safety, pharmacokinetics, and ability of Hu\u2010Mik\u03b21, a humanized monoclonal antibody directed toward the IL\u20102\/IL\u201015 receptor \u03b2\u2010chain (IL\u20102\/IL\u201015R\u03b2: CD122), to saturate CD122 and regulate abnormal immune responses in patients with HAM\/TSP by inhibition of IL\u201015 action.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Hu\u2010Mik\u03b21 was administered intravenously at doses of 0.5\u00a0mg\/kg, 1.0\u00a0mg\/kg, or 1.5\u00a0mg\/kg in a total of nine HAM\/TSP patients. Five doses of Hu\u2010Mik\u03b21 were administered at 3\u2010week intervals. The clinical response was evaluated using standardized scales. Viral and immunologic outcome measures were examined including HTLV\u20101 proviral load, T cell phenotypic analysis and spontaneous lymphoproliferation in HAM\/TSP patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was no significant toxicity associated with Hu\u2010Mik\u03b21 administration in HAM\/TSP patients. Saturation of CD122 by Hu\u2010Mik\u03b21 was achieved in five out of nine HAM\/TSP patients. Administration of Hu\u2010Mik\u03b21 was associated with inhibition of aberrant CD8<jats:sup>+<\/jats:sup> T cell function including spontaneous lymphoproliferation and degranulation and IFN\u2010\u03b3 expression, especially in HAM\/TSP patients that achieved CD122 saturation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>The treatment with Hu\u2010Mik\u03b21 had a number of immunological effects on HAM\/TSP patients although no clinical efficacy was observed. We also did not see any dose\u2010related toxicity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.50820","type":"journal-article","created":{"date-parts":[[2019,7,5]],"date-time":"2019-07-05T07:10:16Z","timestamp":1562310616000},"page":"1383-1394","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Clinical trial of a humanized anti\u2010IL\u20102\/IL\u201015 receptor \u03b2 chain in HAM\/TSP"],"prefix":"10.1002","volume":"6","author":[{"given":"Yoshimi","family":"Enose\u2010Akahata","sequence":"first","affiliation":[{"name":"Viral Immunology Section, Division of Neuroimmunology and Neurovirology, National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Unsong","family":"Oh","sequence":"additional","affiliation":[{"name":"Viral Immunology Section, Division of Neuroimmunology and Neurovirology, National 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