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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2001-12-0295. This Article Full Text (PDF) All Versions of this Article: 2001-12-0295v1 100/9/3101    most recent Alert me when this article is cited Alert me if a correction is posted 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 Borchmann, P. Articles by Engert, A. Search for Related Content PubMed PubMed Citation Articles by Borchmann, P. Articles by Engert, A. Social Bookmarking                   What's this? Submitted January 16, 2002 Accepted May 28, 2002 Phase I trial of the novel bispecific molecule H22xKi-4 in patients with refractory Hodgkin's lymphoma Peter Borchmann, Roland Schnell, Irene Fuss, Oliver Manzke, Thomas Davis, Lionel D Lewis, Claudia Wickenhauser, Petra Schiller, Volker Diehl, and Andreas Engert* Medizinische Klinik I der Universitaet Zu Koeln, Labor fuer Immunotherapie, Koeln, Germany Medarex Inc, Annandale, NJ, USA Dartmouth-Hitchcock Medical Center and Dartmouth Medical School, Lebanon, NH, USA Universitaet Koeln, Institut fuer Pathologie, Koeln, Germany * Corresponding author; email: a.engert{at}uni-koeln.de. Rationale: CD30 is an excellent target for immunotherapy of Hodgkin's lymphoma (HL) since it is overexpressed on Hodgkin and Sternberg-Reed cells. We developed a novel bispecific molecule (BSM) consisting of F(ab`)-fragments derived from the murine anti-CD30 monoclonal antibody (MoAb) Ki-4 and the humanized CD64-specific MoAb H22. In vitro experiments of H22xKi-4 demonstrated specific phagocytosis of HL derived cell lines. Objectives: Patients (pts) with refractory CD30+ HL were treated with escalating doses of H22xKi-4 at doses of 1, 2.5, 5, 10 and 20 mg/m2/d, respectively (administered intravenously on days 1, 3, 5 and 7). The main study objectives were to determine the maximum tolerated dose and the dose limiting toxicities of H22xKi-4, to define its pharmacokinetic profile, and to document clinical response. Results: Ten pts were enrolled and are evaluable for toxicity and response. Side effects were transient and mild with hypotension (4/10), tachycardia (6/10), fatigue (10/10), and fever (2/10 grade-I, 3/10 grade-II). PK data revealed an elimination-half-life of 11.1 hours, resulting in a significant accumulation of H22xKi-4. The BSM was shown to bind to both, monocytes and malignant cells. Response to H22xKi-4 included 1 CR, 3 PR, and 4 pts with stable disease. Conclusions: The new BSM H22xKi-4 can be given safely to pts with refractory CD30+ HL in doses up to 80 mg/m2 per cycle. Although this dose is not the MTD as defined by toxicity-criteria, surrogate parameters suggest a biological effective regimen. H22xKi-4 shows activity in heavily pretreated HL patients warranting further clinical evaluation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. M. Cardarelli, M.-C. Moldovan-Loomis, B. Preston, A. Black, D. Passmore, T.-H. Chen, S. Chen, J. Liu, M. R. Kuhne, M. Srinivasan, et al. In vitro and In vivo Characterization of MDX-1401 for Therapy of Malignant Lymphoma Clin. Cancer Res., May 15, 2009; 15(10): 3376 - 3383. [Abstract] [Full Text] [PDF] B. Stahnke, T. Thepen, M. Stocker, R. Rosinke, E. Jost, R. Fischer, M. K. Tur, and S. Barth Granzyme B-H22(scFv), a human immunotoxin targeting CD64 in acute myeloid leukemia of monocytic subtypes Mol. 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