{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:11:47Z","timestamp":1790424707586,"version":"4.1.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"2","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,1,10]]},"abstract":"<jats:p>Twelve patients with T cell large granular lymphocyte leukemia and associated hematocytopenia were treated in a phase I dose-escalation trial with the murine monoclonal antibody Mik\u03b21. Mik\u03b21 identifies CD122, the \u03b2-subunit shared by the IL-2 and IL-15 receptors. At the doses administered in this study the antibody inhibited the actions of IL-15 on both natural killer and T cells and that of IL-2 when the intermediate-affinity IL-2 receptor was expressed. Mik\u03b21 treatment was not associated with significant toxicity or with the development of an immune response to the infused monoclonal antibody. At these doses of Mik\u03b21, &gt;95% saturation of the IL-2\/IL-15\u03b2 receptor (CD122) on the surfaces of the leukemic cells was achieved. Furthermore, in seven patients this led to the down-modulation of the receptor from the surfaces of the leukemic cells. Nevertheless, no patients manifested a reduction in peripheral leukemic cell count or an amelioration of their hematocytopenia. This latter observation may reflect the fact that the monoclonal T cell large granular lymphocyte leukemia leukemic cells of the patients did not produce IL-2 or IL-15 or require their actions for cell survival. In light of the lack of toxicity and lack of immunogenicity of the antibody observed in the present study and the role for IL-15 in the pathogenesis of autoimmune diseases, clinical trials should be performed using the humanized version of Mik\u03b21 in groups of patients with human T cell lymphotropic virus I-associated myelopathy\/tropical spastic paraparesis, rheumatoid arthritis, multiple sclerosis and refractory celiac disease.<\/jats:p>","DOI":"10.1073\/pnas.0509575103","type":"journal-article","created":{"date-parts":[[2005,12,30]],"date-time":"2005-12-30T20:24:39Z","timestamp":1135974279000},"page":"401-406","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":64,"title":["Preclinical and phase I clinical trial of blockade of IL-15 using Mik\u03b21 monoclonal antibody in T cell large granular lymphocyte leukemia"],"prefix":"10.1073","volume":"103","author":[{"given":"John C.","family":"Morris","sequence":"first","affiliation":[{"name":"Metabolism Branch, Center for Cancer Research, and Office of Cancer Complementary and Alternative Medicine, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892; and Department of Internal Medicine 3, Osaka Red Cross Hospital, Osaka 543-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Janik","sequence":"additional","affiliation":[{"name":"Metabolism Branch, Center for Cancer Research, and Office of Cancer Complementary and Alternative Medicine, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892; and Department of Internal Medicine 3, Osaka Red Cross Hospital, Osaka 543-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"White","sequence":"additional","affiliation":[{"name":"Metabolism Branch, Center for Cancer Research, and Office of Cancer Complementary and Alternative Medicine, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892; and Department of Internal Medicine 3, Osaka Red Cross Hospital, Osaka 543-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Fleisher","sequence":"additional","affiliation":[{"name":"Metabolism Branch, Center for Cancer Research, and Office of Cancer Complementary and Alternative Medicine, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892; and Department of Internal Medicine 3, Osaka Red Cross Hospital, Osaka 543-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Brown","sequence":"additional","affiliation":[{"name":"Metabolism Branch, Center for Cancer Research, and Office of Cancer Complementary and Alternative Medicine, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892; and Department of Internal Medicine 3, Osaka Red Cross Hospital, Osaka 543-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Tsudo","sequence":"additional","affiliation":[{"name":"Metabolism Branch, Center for Cancer Research, and Office of Cancer Complementary and Alternative Medicine, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892; and Department of Internal Medicine 3, Osaka Red Cross Hospital, Osaka 543-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn K.","family":"Goldman","sequence":"additional","affiliation":[{"name":"Metabolism Branch, Center for Cancer Research, and Office of Cancer Complementary and Alternative Medicine, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892; and Department of Internal Medicine 3, Osaka Red Cross Hospital, Osaka 543-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonita","family":"Bryant","sequence":"additional","affiliation":[{"name":"Metabolism Branch, Center for Cancer Research, and Office of Cancer Complementary and Alternative Medicine, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892; and Department of Internal Medicine 3, Osaka Red Cross Hospital, Osaka 543-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Petrus","sequence":"additional","affiliation":[{"name":"Metabolism Branch, Center for Cancer Research, and Office of Cancer Complementary and Alternative Medicine, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892; and Department of Internal Medicine 3, Osaka Red Cross Hospital, Osaka 543-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lois","family":"Top","sequence":"additional","affiliation":[{"name":"Metabolism Branch, Center for Cancer Research, and Office of Cancer Complementary and Alternative Medicine, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892; and Department of Internal Medicine 3, Osaka Red Cross Hospital, Osaka 543-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathryn C.","family":"Lee","sequence":"additional","affiliation":[{"name":"Metabolism Branch, Center for Cancer Research, and Office of Cancer Complementary and Alternative Medicine, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892; and Department of Internal Medicine 3, Osaka Red Cross Hospital, Osaka 543-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Gao","sequence":"additional","affiliation":[{"name":"Metabolism Branch, Center for Cancer Research, and Office of Cancer Complementary and Alternative Medicine, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892; and Department of Internal Medicine 3, Osaka Red Cross Hospital, Osaka 543-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Waldmann","sequence":"additional","affiliation":[{"name":"Metabolism Branch, Center for Cancer Research, and Office of Cancer Complementary and Alternative Medicine, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892; and Department of Internal Medicine 3, Osaka Red Cross Hospital, Osaka 543-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,12,30]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.11.4940"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8178155"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.17.1.19"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00093-0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.200363097"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80564-6"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5466.675"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.1.14"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00429-6"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.8.1187"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0297-189"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200318986"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)01047-3"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.251540598"},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"5654","DOI":"10.4049\/jimmunol.160.11.5654","volume":"160","year":"1998","unstructured":"Ruchatz, H., Leung, B. P., Wei, X. Q., McInnes, I. B. & Liew, F. Y. (1998) J. Immunol. 160, 5654-5660.9605172","journal-title":"J. Immunol."},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"5742","DOI":"10.4049\/jimmunol.160.12.5742","volume":"160","year":"1998","unstructured":"Kim, Y. S., Maslinski, W., Zheng, X. X., Stevens, A. C., Li, X. C., Tesch, G. H., Kelley, V. R. & Strom, T. B. (1998) J. Immunol. 160, 5742-5748.9637483","journal-title":"J. Immunol."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.6.1982"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.4049\/jimmunol.151.2.1075","volume":"151","year":"1993","unstructured":"Hakimi, J., Ha, V. C., Lin, P., Campbell, E., Gately, M. K., Tsudo, M., Payne, P. W., Waldmann, T. A., Grant, A. J., Tsien, W.-H. & Schneider, W. P. (1993) J. Immunol. 151, 1075-1085.8335891","journal-title":"J. Immunol."},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"4330","DOI":"10.4049\/jimmunol.153.9.4330","volume":"153","year":"1994","unstructured":"Tinubu, S. A., Hakimi, J., Kondas, J. A., Bailon, P., Familletti, P. C., Spence, C., Crittenden, M. D., Parenteau, G. L., Dirbas, F. M., Tsudo, M., et al. (1994) J. Immunol. 153, 4330-4338.7930631","journal-title":"J. Immunol."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.1.1.bloodjournal8211"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-198709000-00005"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(75)92127-3"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V75.4.935.935"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V71.4.1161.1161"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.15.5394"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198509263131303"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V74.1.285.285"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19871215)60:12<2971::AID-CNCR2820601220>3.0.CO;2-O"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V76.10.2080.2080"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.5332"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb00035.x"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"452","DOI":"10.4049\/jimmunol.158.1.452","volume":"158","year":"1997","unstructured":"Guex-Crosier, Y., Raber, J., Chan, C. C., Kriete, M., Levin, W., Kersin, J. A., Pilson, R. S., Waldmann, T. A., Hakimi, J. & Roberge, F. G. (1997) J. Immunol. 158, 452-458.8977222","journal-title":"J. Immunol."},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.13.5218"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199801153380304"},{"key":"e_1_3_2_35_2","first-page":"193","volume":"111","year":"1998","unstructured":"Kivisakk, P., Matusevicius, D., He, B., Soderstrom, M., Frederikson, S. & Link, H. (1998) Clin. Exp. Immunol. 111, 193-197.9472681","journal-title":"Clin. Exp. Immunol."},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)01047-3"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.14.1.397"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.6.1701.1701"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0509575103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T21:44:58Z","timestamp":1683323098000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0509575103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,12,30]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2006,1,10]]}},"alternative-id":["10.1073\/pnas.0509575103"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0509575103","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,12,30]]},"assertion":[{"value":"2005-12-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}