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Blood, 15 January 2005, Vol. 105, No. 2, pp. 562-566. Prepublished online as a Blood First Edition Paper on September 16, 2004; DOI 10.1182/blood-2004-04-1482. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1482v1 105/2/562    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Orita, T. Articles by Tsuchiya, M. Search for Related Content PubMed PubMed Citation Articles by Orita, T. Articles by Tsuchiya, M. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS A novel therapeutic approach for thrombocytopenia by minibody agonist of the thrombopoietin receptor Tetsuro Orita, Hiroyuki Tsunoda, Naohiro Yabuta, Kiyotaka Nakano, Takeshi Yoshino, Yuichi Hirata, Toshihiko Ohtomo, Jun-ichi Nezu, Hirofumi Sakumoto, Kouichiro Ono, Mikiyoshi Saito, Eiji Kumagai, Masahiko Nanami, Akihisa Kaneko, Takashi Yoshikubo, and Masayuki Tsuchiya From the Chugai Pharmaceutical Co Ltd, Fuji-Gotemba Research Laboratory, Shizuoka, Japan. Antibodies have brought valuable therapeutics in the clinical treatment of various diseases without serious adverse effects through their intrinsic features such as specific binding to the target antigen with high affinity, clinical safety as serum proteins, and long half-life. Agonist antibodies, furthermore, could be expected to maximize the value of therapeutic antibodies. Indeed, several IgG/IgM antibodies have been reported to induce cellular growth/differentiation and apoptosis. These agonist antibodies, however, should be further improved to exert more potent biologic activities and appropriate serum half-life depending upon the disease indications. Here, we report that IgG antibodies against the thrombopoietin receptor (Mpl), which have an absence or very weak agonist activity, can be engineered to be agonist minibodies, which include diabody or sc(Fv)2 as potent as natural ligand. Through this technological development, minibodies have been successfully constructed to bind and activate 2 types of dysfunctional mutant Mpls that cause congenital amegakaryocytic thrombocytopenia (CAMT). This drastic conversion of biologic activities by designing minibodies can be widely applicable to generate agonist minibodies for clinical application, which will constitute a new paradigm in antibody-based therapeutics. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Minibodies to maximize platelets? Bruce S. Sachais Blood 2005 105: 434-435. [Full Text] [PDF] This article has been cited by other articles: T. B. Gernsheimer The Pathophysiology of ITP Revisited: Ineffective Thrombopoiesis and the Emerging Role of Thrombopoietin Receptor Agonists in the Management of Chronic Immune Thrombocytopenic Purpura Hematology, January 1, 2008; 2008(1): 219 - 226. [Abstract] [Full Text] [PDF] D. J. Kuter New thrombopoietic growth factors Blood, June 1, 2007; 109(11): 4607 - 4616. [Abstract] [Full Text] [PDF] S. Frederickson, M. W. Renshaw, B. Lin, L. M. Smith, P. Calveley, J. P. Springhorn, K. Johnson, Y. Wang, X. Su, Y. Shen, et al. A rationally designed agonist antibody fragment that functionally mimics thrombopoietin PNAS, September 26, 2006; 103(39): 14307 - 14312. [Abstract] [Full Text] [PDF]

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