{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:39:01Z","timestamp":1781109541520,"version":"3.54.1"},"reference-count":22,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,2,17]]},"abstract":"<jats:p>\n                    In patients with malignancies and immune disorders expressing Tac (\u03b1 chain of the interleukin 2 receptor; CD25), physiologic shedding of this receptor may lead to high blood levels of the soluble form (sTac). This system was used to model the interaction of soluble antigen with antibody in therapeutic settings and to develop rational principles to optimize the delivery of antibody to tumor target cells. First, we confirmed that sTac\n                    <jats:italic>in vivo<\/jats:italic>\n                    can block anti-Tac binding sites and diminish antibody binding to Tac+ cells. Second, the bioactivity of antibody\n                    <jats:italic>in vivo<\/jats:italic>\n                    correlated directly with the amount of antibody infused and inversely with the sTac concentration. Third, bindability of antibody declined in the hours and days after anti-Tac infusion in patients. Finally, tumor targeting was achieved even in the presence of excess sTac, demonstrating a partition of antibody between soluble and cell-bound antigen. A role is proposed for the Brambell receptor (FcRB) to delay saturation of human or chimeric antibodies via differential catabolism of antigen\u2013antibody complexes. Principles are developed for predicting activity of administered antibody in the presence of soluble antigen to assist in dose selection in passive, radioimmuno and immunotoxin therapies.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.4.1752","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:40:11Z","timestamp":1027680011000},"page":"1752-1757","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["Impact of antigenemia on the bioactivity of infused anti-Tac antibody: Implications for dose selection in antibody immunotherapies"],"prefix":"10.1073","volume":"95","author":[{"given":"R. P.","family":"Junghans","sequence":"first","affiliation":[{"name":"Biotherapeutics Development Lab, Harvard Medical School, Division of Hematology\u2013Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02115; and Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, and Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. A.","family":"Carrasquillo","sequence":"additional","affiliation":[{"name":"Biotherapeutics Development Lab, Harvard Medical School, Division of Hematology\u2013Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02115; and Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, and Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. A.","family":"Waldmann","sequence":"additional","affiliation":[{"name":"Biotherapeutics Development Lab, Harvard Medical School, Division of Hematology\u2013Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02115; and Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, and Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1998,2,17]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(74)80061-4"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.1860030609"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.annonc.a058593"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198310133091503"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910390113"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V65.6.1349.bloodjournal6561349"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-105-4-560"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-116-2-148"},{"key":"e_1_3_3_9_2","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.4049\/jimmunol.139.7.2308","volume":"139","author":"Jacques Y","year":"1987","unstructured":"Y Jacques, B LeMauff, F Boeffard, A Godard, J P Soulillou J Immunol 139, 2308\u20132316 (1987).","journal-title":"J Immunol"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.4.1587"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.6.1701.1701"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.11.4063.bloodjournal86114063"},{"key":"e_1_3_3_13_2","first-page":"2639","volume":"49","author":"Kozak R W","year":"1989","unstructured":"R W Kozak, A Raubitschek, S Mirzadeh, M W Brechbiel, R P Junghans, O A Gansow, T A Waldmann Cancer Res 49, 2639\u20132644 (1989).","journal-title":"Cancer Res"},{"key":"e_1_3_3_14_2","first-page":"1495","volume":"50","author":"Junghans R P","year":"1990","unstructured":"R P Junghans, T A Waldmann, N F Landolfi, N M Avdalovic, W P Schneider, C Queen Cancer Res 50, 1495\u20131502 (1990).","journal-title":"Cancer Res"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.18.10453"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI104392"},{"key":"e_1_3_3_17_2","first-page":"1","volume":"13","author":"Waldmann T A","year":"1969","unstructured":"T A Waldmann, W Strober Prog Allergy 13, 1\u2013110 (1969).","journal-title":"Prog Allergy"},{"key":"e_1_3_3_18_2","first-page":"161","volume":"20","author":"Cohen S","year":"1961","unstructured":"S Cohen, T Freeman, A S McFarlane Clin Sci (Lond) 20, 161\u2013170 (1961).","journal-title":"Clin Sci (Lond)"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V71.3.640.640"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.160.4.1126"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.11.5512"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02786322"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.95.4.1752","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T08:27:12Z","timestamp":1682152032000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.95.4.1752"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,2,17]]},"references-count":22,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1998,2,17]]}},"alternative-id":["10.1073\/pnas.95.4.1752"],"URL":"https:\/\/doi.org\/10.1073\/pnas.95.4.1752","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,2,17]]},"assertion":[{"value":"1997-12-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-02-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}